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COVID update: ASH experts discuss thrombosis, immunity
NEW ORLEANS –
In a presidential symposium at the annual meeting of the American Society of Hematology, La Jolla Institute of Immunology scientist Shane Crotty, PhD, explained that COVID-19 has a “superpower” that allows it to be “extraordinarily stealthy.”
The virus, he said, can sneak past the body’s innate immune system, which normally responds to viral invaders within minutes to hours. “This is why you have people with high viral loads who are presymptomatic. Their innate immune system hasn’t even recognized that these people are infected.”
The adaptive immune system kicks in later. As Dr. Crotty noted, adaptive immunity is composed of three branches: B cells (the source of antibodies), CD4 “helper” T cells, and CD8 “killer” T cells. In the first year of COVID-19, his team tracked 188 subjects post infection in what he said was the largest study of its kind ever for any viral infection.
“In 8 months, 95% of people who had been infected still had measurable immune memory. In fact, most of them had multiple different compartments of immune memory still detectable, and it was likely that these individuals would still have that memory years into the future. Based on that, we made the prediction that most people who have had COVID-19 would likely be protected from reinfection – at least by severe infections – for 3 years into the future. That prediction has widely held up even in the presence of variants which weren’t around at the time.”
How do vaccines fit into the immunity picture? Dr. Crotty’s lab has tracked subjects who received 4 vaccines – Moderna, Pfizer/BioNTech, Janssen/Johnson & Johnson, and Novavax. Researchers found that the mRNA vaccines, Moderna and Pfizer/BioNTech, “are fantastic at eliciting neutralizing antibodies quickly, but then they drop off rapidly at two doses and actually continue to drop for 10 months.”
Still, he said, “when we take a look at 6 months, actually the vaccines are doing pretty incredibly well. If we compare them to an average infected individual, the mRNA vaccines all have higher neutralizing antibody titers.”
What’s happening? According to Dr. Crotty, B cells are “making guesses about what other variants might look like.” But he said research suggests that an important component of this process – germinal centers – aren’t made in some vaccinated people who are immunocompromised. (Germinal centers have been described as “microbial boot camps” for B cells.)
The good news, Dr. Crotty noted, is that a greater understanding of how COVID-19 penetrates various layers of adaptive immune defenses will lead to better ways to protect the immunocompromised. “If you think about immunity in this layered defense way, there are various ways that it could be enhanced for individuals in different categories,” he said.
Hematologist Beverley J. Hunt, MD, OBE, of St. Thomas’ Hospital/King’s Healthcare Partners in London, spoke at the ASH presidential symposium about blood clots and COVID-19. As she noted, concern arose about vaccine-related blood clots. A British team “managed quickly to come up with a diagnostic criteria,” she said. “We looked at nearly 300 patients and essentially came up with a scoring system.”
The diagnostic criteria was based on an analysis of definite or probable cases of vaccine-induced immune thrombocytopenia and thrombosis (VITT) – all related to the AstraZeneca vaccine. The criteria appeared in a 2021 study in the New England Journal of Medicine.
The report’s data didn’t allow it to compare the efficacy of anticoagulants. However, Dr. Hunt noted that clinicians turned to plasma exchange in patients with low platelet counts and extensive thrombosis. The report stated “survival after plasma exchange was 90%, considerably better than would be predicted given the baseline characteristics.”
“Now we’re following up,” Dr. Hunt said. One question to answer: Is long-term anticoagulation helpful? “We have many patients,” she said, “who are taking an anti-platelet factor out of habit.”
Dr. Crotty and Dr. Hunt report no disclosures. This reporter is a paid participant in a COVID vaccine study run by Dr. Crotty’s lab.
NEW ORLEANS –
In a presidential symposium at the annual meeting of the American Society of Hematology, La Jolla Institute of Immunology scientist Shane Crotty, PhD, explained that COVID-19 has a “superpower” that allows it to be “extraordinarily stealthy.”
The virus, he said, can sneak past the body’s innate immune system, which normally responds to viral invaders within minutes to hours. “This is why you have people with high viral loads who are presymptomatic. Their innate immune system hasn’t even recognized that these people are infected.”
The adaptive immune system kicks in later. As Dr. Crotty noted, adaptive immunity is composed of three branches: B cells (the source of antibodies), CD4 “helper” T cells, and CD8 “killer” T cells. In the first year of COVID-19, his team tracked 188 subjects post infection in what he said was the largest study of its kind ever for any viral infection.
“In 8 months, 95% of people who had been infected still had measurable immune memory. In fact, most of them had multiple different compartments of immune memory still detectable, and it was likely that these individuals would still have that memory years into the future. Based on that, we made the prediction that most people who have had COVID-19 would likely be protected from reinfection – at least by severe infections – for 3 years into the future. That prediction has widely held up even in the presence of variants which weren’t around at the time.”
How do vaccines fit into the immunity picture? Dr. Crotty’s lab has tracked subjects who received 4 vaccines – Moderna, Pfizer/BioNTech, Janssen/Johnson & Johnson, and Novavax. Researchers found that the mRNA vaccines, Moderna and Pfizer/BioNTech, “are fantastic at eliciting neutralizing antibodies quickly, but then they drop off rapidly at two doses and actually continue to drop for 10 months.”
Still, he said, “when we take a look at 6 months, actually the vaccines are doing pretty incredibly well. If we compare them to an average infected individual, the mRNA vaccines all have higher neutralizing antibody titers.”
What’s happening? According to Dr. Crotty, B cells are “making guesses about what other variants might look like.” But he said research suggests that an important component of this process – germinal centers – aren’t made in some vaccinated people who are immunocompromised. (Germinal centers have been described as “microbial boot camps” for B cells.)
The good news, Dr. Crotty noted, is that a greater understanding of how COVID-19 penetrates various layers of adaptive immune defenses will lead to better ways to protect the immunocompromised. “If you think about immunity in this layered defense way, there are various ways that it could be enhanced for individuals in different categories,” he said.
Hematologist Beverley J. Hunt, MD, OBE, of St. Thomas’ Hospital/King’s Healthcare Partners in London, spoke at the ASH presidential symposium about blood clots and COVID-19. As she noted, concern arose about vaccine-related blood clots. A British team “managed quickly to come up with a diagnostic criteria,” she said. “We looked at nearly 300 patients and essentially came up with a scoring system.”
The diagnostic criteria was based on an analysis of definite or probable cases of vaccine-induced immune thrombocytopenia and thrombosis (VITT) – all related to the AstraZeneca vaccine. The criteria appeared in a 2021 study in the New England Journal of Medicine.
The report’s data didn’t allow it to compare the efficacy of anticoagulants. However, Dr. Hunt noted that clinicians turned to plasma exchange in patients with low platelet counts and extensive thrombosis. The report stated “survival after plasma exchange was 90%, considerably better than would be predicted given the baseline characteristics.”
“Now we’re following up,” Dr. Hunt said. One question to answer: Is long-term anticoagulation helpful? “We have many patients,” she said, “who are taking an anti-platelet factor out of habit.”
Dr. Crotty and Dr. Hunt report no disclosures. This reporter is a paid participant in a COVID vaccine study run by Dr. Crotty’s lab.
NEW ORLEANS –
In a presidential symposium at the annual meeting of the American Society of Hematology, La Jolla Institute of Immunology scientist Shane Crotty, PhD, explained that COVID-19 has a “superpower” that allows it to be “extraordinarily stealthy.”
The virus, he said, can sneak past the body’s innate immune system, which normally responds to viral invaders within minutes to hours. “This is why you have people with high viral loads who are presymptomatic. Their innate immune system hasn’t even recognized that these people are infected.”
The adaptive immune system kicks in later. As Dr. Crotty noted, adaptive immunity is composed of three branches: B cells (the source of antibodies), CD4 “helper” T cells, and CD8 “killer” T cells. In the first year of COVID-19, his team tracked 188 subjects post infection in what he said was the largest study of its kind ever for any viral infection.
“In 8 months, 95% of people who had been infected still had measurable immune memory. In fact, most of them had multiple different compartments of immune memory still detectable, and it was likely that these individuals would still have that memory years into the future. Based on that, we made the prediction that most people who have had COVID-19 would likely be protected from reinfection – at least by severe infections – for 3 years into the future. That prediction has widely held up even in the presence of variants which weren’t around at the time.”
How do vaccines fit into the immunity picture? Dr. Crotty’s lab has tracked subjects who received 4 vaccines – Moderna, Pfizer/BioNTech, Janssen/Johnson & Johnson, and Novavax. Researchers found that the mRNA vaccines, Moderna and Pfizer/BioNTech, “are fantastic at eliciting neutralizing antibodies quickly, but then they drop off rapidly at two doses and actually continue to drop for 10 months.”
Still, he said, “when we take a look at 6 months, actually the vaccines are doing pretty incredibly well. If we compare them to an average infected individual, the mRNA vaccines all have higher neutralizing antibody titers.”
What’s happening? According to Dr. Crotty, B cells are “making guesses about what other variants might look like.” But he said research suggests that an important component of this process – germinal centers – aren’t made in some vaccinated people who are immunocompromised. (Germinal centers have been described as “microbial boot camps” for B cells.)
The good news, Dr. Crotty noted, is that a greater understanding of how COVID-19 penetrates various layers of adaptive immune defenses will lead to better ways to protect the immunocompromised. “If you think about immunity in this layered defense way, there are various ways that it could be enhanced for individuals in different categories,” he said.
Hematologist Beverley J. Hunt, MD, OBE, of St. Thomas’ Hospital/King’s Healthcare Partners in London, spoke at the ASH presidential symposium about blood clots and COVID-19. As she noted, concern arose about vaccine-related blood clots. A British team “managed quickly to come up with a diagnostic criteria,” she said. “We looked at nearly 300 patients and essentially came up with a scoring system.”
The diagnostic criteria was based on an analysis of definite or probable cases of vaccine-induced immune thrombocytopenia and thrombosis (VITT) – all related to the AstraZeneca vaccine. The criteria appeared in a 2021 study in the New England Journal of Medicine.
The report’s data didn’t allow it to compare the efficacy of anticoagulants. However, Dr. Hunt noted that clinicians turned to plasma exchange in patients with low platelet counts and extensive thrombosis. The report stated “survival after plasma exchange was 90%, considerably better than would be predicted given the baseline characteristics.”
“Now we’re following up,” Dr. Hunt said. One question to answer: Is long-term anticoagulation helpful? “We have many patients,” she said, “who are taking an anti-platelet factor out of habit.”
Dr. Crotty and Dr. Hunt report no disclosures. This reporter is a paid participant in a COVID vaccine study run by Dr. Crotty’s lab.
AT ASH 2022
Immunotherapy drug boosts survival in newly diagnosed ALL
NEW ORLEANS – The immunotherapy drug blinatumomab improves survival as a first-line treatment in certain younger adult patients with B-lineage acute lymphoblastic leukemia, investigators have found. The extremely expensive drug is currently Food and Drug Administration approved for B-lineage ALL in relapsed/refractory cases.
“We feel that this represents a new standard of care for these patients and should be incorporated into their standard therapy,” said lead author and hematologist Mark R. Litzow, MD, of Mayo Clinic in Rochester, Minn., in a news briefing at the annual meeting of the American Society of Hematology.
B-lineage ALL, also known as B-cell ALL, represents 75% of cases of the blood cancer in adults according to the Leukemia & Lymphoma Society. It occurs when there’s an overgrowth of immature white blood cells known as B-cell lymphoblasts. “These are the blast cells that don’t function well and cause these patients to develop infections and bleeding,” Dr. Litzow said.
Treatments include chemotherapy and stem-cell transplants. Blinatumomab, a bispecific T-cell engager molecule, is FDA approved for patients with relapsed/refractory B-lineage ALL and those with morphologic complete remission who still have measurable residual disease (MRD).
As the new study notes, some patients who undergo chemotherapy and reach remission have poor survival outcomes even when there’s no sign of MRD. “Even though we can’t find leukemia in the patients’ bone marrow, it’s still hiding there,” Dr. Litzow said.
The new phase 3, randomized trial aims to determine if adding blinatumomab (Blincyto) to first-line chemotherapy improves outcomes. The drug “brings a normal T cell, part of the immune system, in proximity to a leukemia plasma cell and kills it.”
For the study, researchers from 2013 to 2019 recruited 488 patients aged 30-70 years with newly diagnosed BCR::ABL1 negative B-lineage ALL (median age = 51). The subjects underwent chemotherapy, and then were “randomized to receive an additional four cycles of consolidation chemo or two cycles of blin [blinatumomab] for 28 days each cycle followed by three cycles of consolidation chemo, another 4-week cycle of blinatumomab (third cycle of blinatumomab) followed by an additional cycle of chemo and then a fourth cycle of blinatumomab (step 3),” the researchers reported. “Following completion of consolidation chemo +/– blin, patients were given 2.5 years of POMP [prednisone, vincristine, 6-mercaptopurine, and methotrexate] maintenance therapy timed from the start of the intensification cycle (step 4).”
There were 112 patients in each group. Among MRD-negative patients, 56 patients died – 17 in the blinatumomab arm and 39 in the control arm at the third interim efficacy analysis. At a mean follow-up of 43 months, median overall survival for patients in the blinatumomab arm was not reached vs. 71.4 months in the control group (hazard ratio, 0.42, 95% confidence interval, 0.24-0.75; P = .003).
“The patients that got blinatumomab plus chemotherapy had an improved survival over those that got the standard chemotherapy,” Dr. Litzow said.
Dr. Litzow didn’t discuss the drug’s expense in his presentation. According to a 2019 report, when a daily vial of blinatumomab cost $3,464-$3,815, a treatment course of five month-long cycles could run to $535,000. According to drugs.com, the cost now is $4,740 per vial – more than $660,000 for five cycles.
In an interview, Cleveland Clinic hematologist/oncologist Anjali Advani, MD, said the study is “groundbreaking and one of the most exciting studies to come along in the acute lymphoblastic leukemia field.”
The trial “is one of the first studies to show improvement in outcome in a randomized manner with the addition of a novel agent,” she added. “This will change our standard of care for these patients.”
The National Cancer Institute funded the trial and drug manufacturer Amgen provided the medication and support through a cooperative research and development agreement.
Dr. Litzow discloses relationships with Actinium, Jazz, Syndax, Novartis, Astellas, Amgen, Abbvie, Pluristem and Biosight. Other authors have various disclosures with multiple drugmakers. Dr. Advani discloses relationships with Amgen, Jazz, Nkarta, Taiho, Beam, GMI, Kura, Pfizer, OBI, Incyte, Kite, ImmunoGen, GlycoMimetics, SGN, MacroGenics, and Servier.
NEW ORLEANS – The immunotherapy drug blinatumomab improves survival as a first-line treatment in certain younger adult patients with B-lineage acute lymphoblastic leukemia, investigators have found. The extremely expensive drug is currently Food and Drug Administration approved for B-lineage ALL in relapsed/refractory cases.
“We feel that this represents a new standard of care for these patients and should be incorporated into their standard therapy,” said lead author and hematologist Mark R. Litzow, MD, of Mayo Clinic in Rochester, Minn., in a news briefing at the annual meeting of the American Society of Hematology.
B-lineage ALL, also known as B-cell ALL, represents 75% of cases of the blood cancer in adults according to the Leukemia & Lymphoma Society. It occurs when there’s an overgrowth of immature white blood cells known as B-cell lymphoblasts. “These are the blast cells that don’t function well and cause these patients to develop infections and bleeding,” Dr. Litzow said.
Treatments include chemotherapy and stem-cell transplants. Blinatumomab, a bispecific T-cell engager molecule, is FDA approved for patients with relapsed/refractory B-lineage ALL and those with morphologic complete remission who still have measurable residual disease (MRD).
As the new study notes, some patients who undergo chemotherapy and reach remission have poor survival outcomes even when there’s no sign of MRD. “Even though we can’t find leukemia in the patients’ bone marrow, it’s still hiding there,” Dr. Litzow said.
The new phase 3, randomized trial aims to determine if adding blinatumomab (Blincyto) to first-line chemotherapy improves outcomes. The drug “brings a normal T cell, part of the immune system, in proximity to a leukemia plasma cell and kills it.”
For the study, researchers from 2013 to 2019 recruited 488 patients aged 30-70 years with newly diagnosed BCR::ABL1 negative B-lineage ALL (median age = 51). The subjects underwent chemotherapy, and then were “randomized to receive an additional four cycles of consolidation chemo or two cycles of blin [blinatumomab] for 28 days each cycle followed by three cycles of consolidation chemo, another 4-week cycle of blinatumomab (third cycle of blinatumomab) followed by an additional cycle of chemo and then a fourth cycle of blinatumomab (step 3),” the researchers reported. “Following completion of consolidation chemo +/– blin, patients were given 2.5 years of POMP [prednisone, vincristine, 6-mercaptopurine, and methotrexate] maintenance therapy timed from the start of the intensification cycle (step 4).”
There were 112 patients in each group. Among MRD-negative patients, 56 patients died – 17 in the blinatumomab arm and 39 in the control arm at the third interim efficacy analysis. At a mean follow-up of 43 months, median overall survival for patients in the blinatumomab arm was not reached vs. 71.4 months in the control group (hazard ratio, 0.42, 95% confidence interval, 0.24-0.75; P = .003).
“The patients that got blinatumomab plus chemotherapy had an improved survival over those that got the standard chemotherapy,” Dr. Litzow said.
Dr. Litzow didn’t discuss the drug’s expense in his presentation. According to a 2019 report, when a daily vial of blinatumomab cost $3,464-$3,815, a treatment course of five month-long cycles could run to $535,000. According to drugs.com, the cost now is $4,740 per vial – more than $660,000 for five cycles.
In an interview, Cleveland Clinic hematologist/oncologist Anjali Advani, MD, said the study is “groundbreaking and one of the most exciting studies to come along in the acute lymphoblastic leukemia field.”
The trial “is one of the first studies to show improvement in outcome in a randomized manner with the addition of a novel agent,” she added. “This will change our standard of care for these patients.”
The National Cancer Institute funded the trial and drug manufacturer Amgen provided the medication and support through a cooperative research and development agreement.
Dr. Litzow discloses relationships with Actinium, Jazz, Syndax, Novartis, Astellas, Amgen, Abbvie, Pluristem and Biosight. Other authors have various disclosures with multiple drugmakers. Dr. Advani discloses relationships with Amgen, Jazz, Nkarta, Taiho, Beam, GMI, Kura, Pfizer, OBI, Incyte, Kite, ImmunoGen, GlycoMimetics, SGN, MacroGenics, and Servier.
NEW ORLEANS – The immunotherapy drug blinatumomab improves survival as a first-line treatment in certain younger adult patients with B-lineage acute lymphoblastic leukemia, investigators have found. The extremely expensive drug is currently Food and Drug Administration approved for B-lineage ALL in relapsed/refractory cases.
“We feel that this represents a new standard of care for these patients and should be incorporated into their standard therapy,” said lead author and hematologist Mark R. Litzow, MD, of Mayo Clinic in Rochester, Minn., in a news briefing at the annual meeting of the American Society of Hematology.
B-lineage ALL, also known as B-cell ALL, represents 75% of cases of the blood cancer in adults according to the Leukemia & Lymphoma Society. It occurs when there’s an overgrowth of immature white blood cells known as B-cell lymphoblasts. “These are the blast cells that don’t function well and cause these patients to develop infections and bleeding,” Dr. Litzow said.
Treatments include chemotherapy and stem-cell transplants. Blinatumomab, a bispecific T-cell engager molecule, is FDA approved for patients with relapsed/refractory B-lineage ALL and those with morphologic complete remission who still have measurable residual disease (MRD).
As the new study notes, some patients who undergo chemotherapy and reach remission have poor survival outcomes even when there’s no sign of MRD. “Even though we can’t find leukemia in the patients’ bone marrow, it’s still hiding there,” Dr. Litzow said.
The new phase 3, randomized trial aims to determine if adding blinatumomab (Blincyto) to first-line chemotherapy improves outcomes. The drug “brings a normal T cell, part of the immune system, in proximity to a leukemia plasma cell and kills it.”
For the study, researchers from 2013 to 2019 recruited 488 patients aged 30-70 years with newly diagnosed BCR::ABL1 negative B-lineage ALL (median age = 51). The subjects underwent chemotherapy, and then were “randomized to receive an additional four cycles of consolidation chemo or two cycles of blin [blinatumomab] for 28 days each cycle followed by three cycles of consolidation chemo, another 4-week cycle of blinatumomab (third cycle of blinatumomab) followed by an additional cycle of chemo and then a fourth cycle of blinatumomab (step 3),” the researchers reported. “Following completion of consolidation chemo +/– blin, patients were given 2.5 years of POMP [prednisone, vincristine, 6-mercaptopurine, and methotrexate] maintenance therapy timed from the start of the intensification cycle (step 4).”
There were 112 patients in each group. Among MRD-negative patients, 56 patients died – 17 in the blinatumomab arm and 39 in the control arm at the third interim efficacy analysis. At a mean follow-up of 43 months, median overall survival for patients in the blinatumomab arm was not reached vs. 71.4 months in the control group (hazard ratio, 0.42, 95% confidence interval, 0.24-0.75; P = .003).
“The patients that got blinatumomab plus chemotherapy had an improved survival over those that got the standard chemotherapy,” Dr. Litzow said.
Dr. Litzow didn’t discuss the drug’s expense in his presentation. According to a 2019 report, when a daily vial of blinatumomab cost $3,464-$3,815, a treatment course of five month-long cycles could run to $535,000. According to drugs.com, the cost now is $4,740 per vial – more than $660,000 for five cycles.
In an interview, Cleveland Clinic hematologist/oncologist Anjali Advani, MD, said the study is “groundbreaking and one of the most exciting studies to come along in the acute lymphoblastic leukemia field.”
The trial “is one of the first studies to show improvement in outcome in a randomized manner with the addition of a novel agent,” she added. “This will change our standard of care for these patients.”
The National Cancer Institute funded the trial and drug manufacturer Amgen provided the medication and support through a cooperative research and development agreement.
Dr. Litzow discloses relationships with Actinium, Jazz, Syndax, Novartis, Astellas, Amgen, Abbvie, Pluristem and Biosight. Other authors have various disclosures with multiple drugmakers. Dr. Advani discloses relationships with Amgen, Jazz, Nkarta, Taiho, Beam, GMI, Kura, Pfizer, OBI, Incyte, Kite, ImmunoGen, GlycoMimetics, SGN, MacroGenics, and Servier.
AT ASH 2022
Study: Formula-fed extreme preemies need more iron
NEW ORLEANS –
“We were surprised that, despite actually receiving more iron in total each day on average, the formula-fed infants were significantly more iron deficient than breast-fed babies. This is the opposite of what one would expect,” study lead author Grace Power, a medical student at Dalhousie University, Halifax, N.S., said in an interview. She presented the results at the annual meeting of the American Society of Hematology.
According to Ms. Power, there’s limited research into how breastfeeding and formula feeding affect iron levels in preterm infants – especially those born extremely early, between 23 and 30 weeks’ gestation.
“This kind of research is important because preterm infants are highly susceptible to iron deficiency for a number of reasons,” she said. “Iron deficiency early in life is associated with developmental and behavioral problems later on in life. That association still stands, even if the iron deficiency is corrected, so prevention is key in this population. Knowing more about how feeding type affects iron status can help us learn about ways to prevent iron deficiency in these infants in the future.”
For the study, researchers retrospectively analyzed data about all preterm infants (< 31 weeks gestation) in Nova Scotia from 2005 to 2018. Of the 392 infants in this group (55.75% male; average age, about 5 months), 285 were fed with iron-rich formula (mean intake, 1.66 mg/kg per day), and 107 were fully or partially breast fed. The two groups were similar in terms of traits such as mean birth weight and gestational age.
The formula-fed infants were more likely to develop iron deficiency (ID, 36.8%) than the breast-fed infants (20.6%; P = .002). “Mean gestational age and birth weight were both lower in the ID group. The ID group also had a higher percentage of infants born less than 1,100 g (P = .01). More babies in the ID group received at least one blood transfusion,” the researchers reported. “ID infants had a higher daily formula intake, daily iron intake from formula, and total daily iron intake combined from formula and supplements.”
Why is there such a gap between formula-fed infants and breast-fed infants? The researchers speculated that infants absorb less iron from formula versus breast milk, possibly because of the presence of lactoferrin in breast milk.
The researchers also wondered whether physicians may pull back on iron supplementation in infants who undergo blood transfusions out of fear of the risk of iron overload, which Ms. Power said can cause infection and poor growth. By doing so, they may inadvertently deprive the babies of their need for iron.
“We don’t want clinicians to assume an infant doesn’t need iron supplementation just because they’ve received a blood transfusion,” she said.
As for an overall message from the research, Ms. Power said clinicians “should be aware that formula feeding can put infants at risk for iron deficiency and consider this when making decisions about supplementation.” And she noted that guidelines from the American Academy of Pediatrics and Canadian Pediatric Society don’t highlight the importance of iron supplementation in formula-fed, very preterm infants.
In an interview, University of Michigan pediatrician Michael K. Georgieff, MD, who has studied iron supplementation, said the study’s primary findings are surprising, although it makes sense that infants with lower gestational age and birth weight would suffer from more ID. Blood transfusion can indeed raise iron levels, but it’s important to consider that these infants may already have low levels of iron.
Dr. Georgieff advised colleagues to understand the potential for various nutritional deficiencies in preterm infants well beyond the first few weeks. When the babies are handed off to other clinicians such as pediatricians, they should undergo nutritional screening at 6 months, not at a year.
Dalhousie University funded the study. The study authors and Dr. Georgieff have no disclosures.
NEW ORLEANS –
“We were surprised that, despite actually receiving more iron in total each day on average, the formula-fed infants were significantly more iron deficient than breast-fed babies. This is the opposite of what one would expect,” study lead author Grace Power, a medical student at Dalhousie University, Halifax, N.S., said in an interview. She presented the results at the annual meeting of the American Society of Hematology.
According to Ms. Power, there’s limited research into how breastfeeding and formula feeding affect iron levels in preterm infants – especially those born extremely early, between 23 and 30 weeks’ gestation.
“This kind of research is important because preterm infants are highly susceptible to iron deficiency for a number of reasons,” she said. “Iron deficiency early in life is associated with developmental and behavioral problems later on in life. That association still stands, even if the iron deficiency is corrected, so prevention is key in this population. Knowing more about how feeding type affects iron status can help us learn about ways to prevent iron deficiency in these infants in the future.”
For the study, researchers retrospectively analyzed data about all preterm infants (< 31 weeks gestation) in Nova Scotia from 2005 to 2018. Of the 392 infants in this group (55.75% male; average age, about 5 months), 285 were fed with iron-rich formula (mean intake, 1.66 mg/kg per day), and 107 were fully or partially breast fed. The two groups were similar in terms of traits such as mean birth weight and gestational age.
The formula-fed infants were more likely to develop iron deficiency (ID, 36.8%) than the breast-fed infants (20.6%; P = .002). “Mean gestational age and birth weight were both lower in the ID group. The ID group also had a higher percentage of infants born less than 1,100 g (P = .01). More babies in the ID group received at least one blood transfusion,” the researchers reported. “ID infants had a higher daily formula intake, daily iron intake from formula, and total daily iron intake combined from formula and supplements.”
Why is there such a gap between formula-fed infants and breast-fed infants? The researchers speculated that infants absorb less iron from formula versus breast milk, possibly because of the presence of lactoferrin in breast milk.
The researchers also wondered whether physicians may pull back on iron supplementation in infants who undergo blood transfusions out of fear of the risk of iron overload, which Ms. Power said can cause infection and poor growth. By doing so, they may inadvertently deprive the babies of their need for iron.
“We don’t want clinicians to assume an infant doesn’t need iron supplementation just because they’ve received a blood transfusion,” she said.
As for an overall message from the research, Ms. Power said clinicians “should be aware that formula feeding can put infants at risk for iron deficiency and consider this when making decisions about supplementation.” And she noted that guidelines from the American Academy of Pediatrics and Canadian Pediatric Society don’t highlight the importance of iron supplementation in formula-fed, very preterm infants.
In an interview, University of Michigan pediatrician Michael K. Georgieff, MD, who has studied iron supplementation, said the study’s primary findings are surprising, although it makes sense that infants with lower gestational age and birth weight would suffer from more ID. Blood transfusion can indeed raise iron levels, but it’s important to consider that these infants may already have low levels of iron.
Dr. Georgieff advised colleagues to understand the potential for various nutritional deficiencies in preterm infants well beyond the first few weeks. When the babies are handed off to other clinicians such as pediatricians, they should undergo nutritional screening at 6 months, not at a year.
Dalhousie University funded the study. The study authors and Dr. Georgieff have no disclosures.
NEW ORLEANS –
“We were surprised that, despite actually receiving more iron in total each day on average, the formula-fed infants were significantly more iron deficient than breast-fed babies. This is the opposite of what one would expect,” study lead author Grace Power, a medical student at Dalhousie University, Halifax, N.S., said in an interview. She presented the results at the annual meeting of the American Society of Hematology.
According to Ms. Power, there’s limited research into how breastfeeding and formula feeding affect iron levels in preterm infants – especially those born extremely early, between 23 and 30 weeks’ gestation.
“This kind of research is important because preterm infants are highly susceptible to iron deficiency for a number of reasons,” she said. “Iron deficiency early in life is associated with developmental and behavioral problems later on in life. That association still stands, even if the iron deficiency is corrected, so prevention is key in this population. Knowing more about how feeding type affects iron status can help us learn about ways to prevent iron deficiency in these infants in the future.”
For the study, researchers retrospectively analyzed data about all preterm infants (< 31 weeks gestation) in Nova Scotia from 2005 to 2018. Of the 392 infants in this group (55.75% male; average age, about 5 months), 285 were fed with iron-rich formula (mean intake, 1.66 mg/kg per day), and 107 were fully or partially breast fed. The two groups were similar in terms of traits such as mean birth weight and gestational age.
The formula-fed infants were more likely to develop iron deficiency (ID, 36.8%) than the breast-fed infants (20.6%; P = .002). “Mean gestational age and birth weight were both lower in the ID group. The ID group also had a higher percentage of infants born less than 1,100 g (P = .01). More babies in the ID group received at least one blood transfusion,” the researchers reported. “ID infants had a higher daily formula intake, daily iron intake from formula, and total daily iron intake combined from formula and supplements.”
Why is there such a gap between formula-fed infants and breast-fed infants? The researchers speculated that infants absorb less iron from formula versus breast milk, possibly because of the presence of lactoferrin in breast milk.
The researchers also wondered whether physicians may pull back on iron supplementation in infants who undergo blood transfusions out of fear of the risk of iron overload, which Ms. Power said can cause infection and poor growth. By doing so, they may inadvertently deprive the babies of their need for iron.
“We don’t want clinicians to assume an infant doesn’t need iron supplementation just because they’ve received a blood transfusion,” she said.
As for an overall message from the research, Ms. Power said clinicians “should be aware that formula feeding can put infants at risk for iron deficiency and consider this when making decisions about supplementation.” And she noted that guidelines from the American Academy of Pediatrics and Canadian Pediatric Society don’t highlight the importance of iron supplementation in formula-fed, very preterm infants.
In an interview, University of Michigan pediatrician Michael K. Georgieff, MD, who has studied iron supplementation, said the study’s primary findings are surprising, although it makes sense that infants with lower gestational age and birth weight would suffer from more ID. Blood transfusion can indeed raise iron levels, but it’s important to consider that these infants may already have low levels of iron.
Dr. Georgieff advised colleagues to understand the potential for various nutritional deficiencies in preterm infants well beyond the first few weeks. When the babies are handed off to other clinicians such as pediatricians, they should undergo nutritional screening at 6 months, not at a year.
Dalhousie University funded the study. The study authors and Dr. Georgieff have no disclosures.
AT ASH 2022
CLL phase 3 study: Zanubrutinib bests ibrutinib
Progression-free survival (PFS) was significantly higher for zanubrutinib versus ibrutinib, according to investigator Jennifer R. Brown, MD, PhD, director of the Center for Chronic Lymphocytic Leukemia at Dana-Farber Cancer Institute, Boston.
Cardiac safety was also better with zanubrutinib, the second-generation Bruton’s tyrosine kinase inhibitor, compared to ibrutinib, the first-in-class Bruton’s tyrosine kinase inhibitor. Dr. Brown noted that ibrutinib has “transformed CLL therapy,” despite toxicity and pharmacokinetics issues which limit its use.
Even in patients with high-risk CLL, there was a clear benefit of zanubrutinib over ibrutinib, according to Dr. Brown, who presented final results of ALPINE in a late-breaking clinical trials session at the annual meeting of the American Society of Hematology.
“I am not aware of a patient population in which I would select ibrutinib as compared to zanubrutinib,” Dr. Brown said in a press briefing on the study at the meeting.
Although not currently indicated in CLL, zanubrutinib received Food and Drug Administration approval for treatment of relapsed/refractory mantle cell lymphoma in late 2019, followed by indications in Waldenström’s macroglobulinemia and relapsed/refractory marginal zone lymphoma in 2021.
But the choice of zanubrutinib over ibrutinib in relapsed/refractory CLL is already supported in current clinical practice guidelines, Dr. Brown said.
The most recent CLL guidelines from the National Comprehensive Cancer Network (NCCN), updated Aug 30, describe zanubrutinib as a “preferred” regimen, while ibrutinib falls into the category of an “other recommended regimen.”
The zanubrutinib recommendation is category 1, meaning that it is based on high-level evidence, with uniform consensus that the intervention in appropriate, according to NCCN.
Improved safety, efficacy
Side effects have proved to be an Achilles heel for ibrutinib, which first received an FDA approval in CLL in 2014.
Across CLL studies, between 16% and 23% of CLL patients have discontinued ibrutinib treatment because of toxicities, Dr. Brown, the ALPINE investigator, said at the ASH meeting.
In addition, pharmacokinetic data suggest that at certain times between doses, the amount of ibrutinib in a patient’s system may drop below the level needed to effectively inhibit the target protein, Bruton’s tyrosine kinase.
By contrast, zanubrutinib is designed to have greater specificity for that target protein, Dr. Brown said. Furthermore, the pharmacokinetic studies have demonstrated concentrations of drug consistently above the level needed for effective inhibition – an effect that suggests potential for greater efficacy.
In the ALPINE study, 652 patients with relapsed/refractory CLL/small lymphocytic lymphoma (SLL) were randomized to zanubrutinib 160 mg twice daily or ibrutinib once daily.
With a mean follow-up of 29.6 months, zanubrutinib PFS was significantly superior to ibrutinib, according to Dr. Brown, with a hazard ratio (HR) of 0.65 and 95% confidence interval (CI) between 0.49 and 0.86.
Estimated PFS at 2 years was 79.5% in the zanubrutinib arm and 67.3% for ibrutinib, according to the ALPINE data presented.
However, the difference in PFS in favor of zanubrutinib was even more pronounced in high-risk patients, according to Dr. Brown. Among patients with chromosome 17 deletion or TP53 mutation, the PFS at 2 years was 77.6% for zanubrutinib and just 55.7% for ibrutinib, with an HR of 0.52 and 95% CI of 0.30 to 0.88.
Zanubrutinib’s safety profile was superior to ibrutinib, with serious adverse rates of 42.0% and 50.0%, respectively, and significantly lower cardiac toxicity for zanubrutinib, according to the investigators’ presentation.
Only 5.2% of patients on zanubrutinib had atrial fibrillation/flutter on study, compared to 13.3% for ibrutinib (P = .0004), while rates of serious cardiac adverse events were 1.9% and 7.7% , respectively.
Impressive benefit
The PFS benefit of zanubrutinib over ibrutinib was “quite impressive” in ALPINE, and in line with pharmacokinetic differences observed between Bruton’s tyrosine kinase inhibitors, said Stefan K. Barta, MD, associate professor of medicine at the University of Pennsylvania in Philadelphia.
“In the lab, [second-generation Bruton’s tyrosine kinase inhibitors] do hit the target better, but better doesn’t necessarily translate into good outcomes for patients – that’s a different question,” Dr. Barta said in an interview
However, the safety findings of ALPINE are particularly relevant, according to Dr. Barta, since today, many patients with CLL will receive treatment with Bruton’s tyrosine kinase inhibitors indefinitely.
In ALPINE results presented at ASH, zanubrutinib-treated patients had lower rates of atrial fibrillation and serious cardiac events, as well as zero deaths due to cardiac events, compared to six deaths in the ibrutinib group.
“Side effects make a big difference if you are on something for a long time,” Dr. Barta said. “It’s certainly a huge difference already, but then if you get the added bonus of also having an improvement in PFS, that’s a win-win.”
Dr. Brown reported disclosures related to Abbvie, Acerta/AstraZeneca, Beigene, Bristol-Myers Squibb/Juno/Celgene, Catapult, Genentech/Roche, Janssen, MEI Pharma, Morphosys AG, Novartis, Pfizer, Rigel, Gilead, Loxo/Lilly, Verastem/Secura Bio, Sun, TG Therapeutics, Invectys, Grifols Worldwide Operations, Hutchmed, iOnctura, and Pharmacyclics.
Progression-free survival (PFS) was significantly higher for zanubrutinib versus ibrutinib, according to investigator Jennifer R. Brown, MD, PhD, director of the Center for Chronic Lymphocytic Leukemia at Dana-Farber Cancer Institute, Boston.
Cardiac safety was also better with zanubrutinib, the second-generation Bruton’s tyrosine kinase inhibitor, compared to ibrutinib, the first-in-class Bruton’s tyrosine kinase inhibitor. Dr. Brown noted that ibrutinib has “transformed CLL therapy,” despite toxicity and pharmacokinetics issues which limit its use.
Even in patients with high-risk CLL, there was a clear benefit of zanubrutinib over ibrutinib, according to Dr. Brown, who presented final results of ALPINE in a late-breaking clinical trials session at the annual meeting of the American Society of Hematology.
“I am not aware of a patient population in which I would select ibrutinib as compared to zanubrutinib,” Dr. Brown said in a press briefing on the study at the meeting.
Although not currently indicated in CLL, zanubrutinib received Food and Drug Administration approval for treatment of relapsed/refractory mantle cell lymphoma in late 2019, followed by indications in Waldenström’s macroglobulinemia and relapsed/refractory marginal zone lymphoma in 2021.
But the choice of zanubrutinib over ibrutinib in relapsed/refractory CLL is already supported in current clinical practice guidelines, Dr. Brown said.
The most recent CLL guidelines from the National Comprehensive Cancer Network (NCCN), updated Aug 30, describe zanubrutinib as a “preferred” regimen, while ibrutinib falls into the category of an “other recommended regimen.”
The zanubrutinib recommendation is category 1, meaning that it is based on high-level evidence, with uniform consensus that the intervention in appropriate, according to NCCN.
Improved safety, efficacy
Side effects have proved to be an Achilles heel for ibrutinib, which first received an FDA approval in CLL in 2014.
Across CLL studies, between 16% and 23% of CLL patients have discontinued ibrutinib treatment because of toxicities, Dr. Brown, the ALPINE investigator, said at the ASH meeting.
In addition, pharmacokinetic data suggest that at certain times between doses, the amount of ibrutinib in a patient’s system may drop below the level needed to effectively inhibit the target protein, Bruton’s tyrosine kinase.
By contrast, zanubrutinib is designed to have greater specificity for that target protein, Dr. Brown said. Furthermore, the pharmacokinetic studies have demonstrated concentrations of drug consistently above the level needed for effective inhibition – an effect that suggests potential for greater efficacy.
In the ALPINE study, 652 patients with relapsed/refractory CLL/small lymphocytic lymphoma (SLL) were randomized to zanubrutinib 160 mg twice daily or ibrutinib once daily.
With a mean follow-up of 29.6 months, zanubrutinib PFS was significantly superior to ibrutinib, according to Dr. Brown, with a hazard ratio (HR) of 0.65 and 95% confidence interval (CI) between 0.49 and 0.86.
Estimated PFS at 2 years was 79.5% in the zanubrutinib arm and 67.3% for ibrutinib, according to the ALPINE data presented.
However, the difference in PFS in favor of zanubrutinib was even more pronounced in high-risk patients, according to Dr. Brown. Among patients with chromosome 17 deletion or TP53 mutation, the PFS at 2 years was 77.6% for zanubrutinib and just 55.7% for ibrutinib, with an HR of 0.52 and 95% CI of 0.30 to 0.88.
Zanubrutinib’s safety profile was superior to ibrutinib, with serious adverse rates of 42.0% and 50.0%, respectively, and significantly lower cardiac toxicity for zanubrutinib, according to the investigators’ presentation.
Only 5.2% of patients on zanubrutinib had atrial fibrillation/flutter on study, compared to 13.3% for ibrutinib (P = .0004), while rates of serious cardiac adverse events were 1.9% and 7.7% , respectively.
Impressive benefit
The PFS benefit of zanubrutinib over ibrutinib was “quite impressive” in ALPINE, and in line with pharmacokinetic differences observed between Bruton’s tyrosine kinase inhibitors, said Stefan K. Barta, MD, associate professor of medicine at the University of Pennsylvania in Philadelphia.
“In the lab, [second-generation Bruton’s tyrosine kinase inhibitors] do hit the target better, but better doesn’t necessarily translate into good outcomes for patients – that’s a different question,” Dr. Barta said in an interview
However, the safety findings of ALPINE are particularly relevant, according to Dr. Barta, since today, many patients with CLL will receive treatment with Bruton’s tyrosine kinase inhibitors indefinitely.
In ALPINE results presented at ASH, zanubrutinib-treated patients had lower rates of atrial fibrillation and serious cardiac events, as well as zero deaths due to cardiac events, compared to six deaths in the ibrutinib group.
“Side effects make a big difference if you are on something for a long time,” Dr. Barta said. “It’s certainly a huge difference already, but then if you get the added bonus of also having an improvement in PFS, that’s a win-win.”
Dr. Brown reported disclosures related to Abbvie, Acerta/AstraZeneca, Beigene, Bristol-Myers Squibb/Juno/Celgene, Catapult, Genentech/Roche, Janssen, MEI Pharma, Morphosys AG, Novartis, Pfizer, Rigel, Gilead, Loxo/Lilly, Verastem/Secura Bio, Sun, TG Therapeutics, Invectys, Grifols Worldwide Operations, Hutchmed, iOnctura, and Pharmacyclics.
Progression-free survival (PFS) was significantly higher for zanubrutinib versus ibrutinib, according to investigator Jennifer R. Brown, MD, PhD, director of the Center for Chronic Lymphocytic Leukemia at Dana-Farber Cancer Institute, Boston.
Cardiac safety was also better with zanubrutinib, the second-generation Bruton’s tyrosine kinase inhibitor, compared to ibrutinib, the first-in-class Bruton’s tyrosine kinase inhibitor. Dr. Brown noted that ibrutinib has “transformed CLL therapy,” despite toxicity and pharmacokinetics issues which limit its use.
Even in patients with high-risk CLL, there was a clear benefit of zanubrutinib over ibrutinib, according to Dr. Brown, who presented final results of ALPINE in a late-breaking clinical trials session at the annual meeting of the American Society of Hematology.
“I am not aware of a patient population in which I would select ibrutinib as compared to zanubrutinib,” Dr. Brown said in a press briefing on the study at the meeting.
Although not currently indicated in CLL, zanubrutinib received Food and Drug Administration approval for treatment of relapsed/refractory mantle cell lymphoma in late 2019, followed by indications in Waldenström’s macroglobulinemia and relapsed/refractory marginal zone lymphoma in 2021.
But the choice of zanubrutinib over ibrutinib in relapsed/refractory CLL is already supported in current clinical practice guidelines, Dr. Brown said.
The most recent CLL guidelines from the National Comprehensive Cancer Network (NCCN), updated Aug 30, describe zanubrutinib as a “preferred” regimen, while ibrutinib falls into the category of an “other recommended regimen.”
The zanubrutinib recommendation is category 1, meaning that it is based on high-level evidence, with uniform consensus that the intervention in appropriate, according to NCCN.
Improved safety, efficacy
Side effects have proved to be an Achilles heel for ibrutinib, which first received an FDA approval in CLL in 2014.
Across CLL studies, between 16% and 23% of CLL patients have discontinued ibrutinib treatment because of toxicities, Dr. Brown, the ALPINE investigator, said at the ASH meeting.
In addition, pharmacokinetic data suggest that at certain times between doses, the amount of ibrutinib in a patient’s system may drop below the level needed to effectively inhibit the target protein, Bruton’s tyrosine kinase.
By contrast, zanubrutinib is designed to have greater specificity for that target protein, Dr. Brown said. Furthermore, the pharmacokinetic studies have demonstrated concentrations of drug consistently above the level needed for effective inhibition – an effect that suggests potential for greater efficacy.
In the ALPINE study, 652 patients with relapsed/refractory CLL/small lymphocytic lymphoma (SLL) were randomized to zanubrutinib 160 mg twice daily or ibrutinib once daily.
With a mean follow-up of 29.6 months, zanubrutinib PFS was significantly superior to ibrutinib, according to Dr. Brown, with a hazard ratio (HR) of 0.65 and 95% confidence interval (CI) between 0.49 and 0.86.
Estimated PFS at 2 years was 79.5% in the zanubrutinib arm and 67.3% for ibrutinib, according to the ALPINE data presented.
However, the difference in PFS in favor of zanubrutinib was even more pronounced in high-risk patients, according to Dr. Brown. Among patients with chromosome 17 deletion or TP53 mutation, the PFS at 2 years was 77.6% for zanubrutinib and just 55.7% for ibrutinib, with an HR of 0.52 and 95% CI of 0.30 to 0.88.
Zanubrutinib’s safety profile was superior to ibrutinib, with serious adverse rates of 42.0% and 50.0%, respectively, and significantly lower cardiac toxicity for zanubrutinib, according to the investigators’ presentation.
Only 5.2% of patients on zanubrutinib had atrial fibrillation/flutter on study, compared to 13.3% for ibrutinib (P = .0004), while rates of serious cardiac adverse events were 1.9% and 7.7% , respectively.
Impressive benefit
The PFS benefit of zanubrutinib over ibrutinib was “quite impressive” in ALPINE, and in line with pharmacokinetic differences observed between Bruton’s tyrosine kinase inhibitors, said Stefan K. Barta, MD, associate professor of medicine at the University of Pennsylvania in Philadelphia.
“In the lab, [second-generation Bruton’s tyrosine kinase inhibitors] do hit the target better, but better doesn’t necessarily translate into good outcomes for patients – that’s a different question,” Dr. Barta said in an interview
However, the safety findings of ALPINE are particularly relevant, according to Dr. Barta, since today, many patients with CLL will receive treatment with Bruton’s tyrosine kinase inhibitors indefinitely.
In ALPINE results presented at ASH, zanubrutinib-treated patients had lower rates of atrial fibrillation and serious cardiac events, as well as zero deaths due to cardiac events, compared to six deaths in the ibrutinib group.
“Side effects make a big difference if you are on something for a long time,” Dr. Barta said. “It’s certainly a huge difference already, but then if you get the added bonus of also having an improvement in PFS, that’s a win-win.”
Dr. Brown reported disclosures related to Abbvie, Acerta/AstraZeneca, Beigene, Bristol-Myers Squibb/Juno/Celgene, Catapult, Genentech/Roche, Janssen, MEI Pharma, Morphosys AG, Novartis, Pfizer, Rigel, Gilead, Loxo/Lilly, Verastem/Secura Bio, Sun, TG Therapeutics, Invectys, Grifols Worldwide Operations, Hutchmed, iOnctura, and Pharmacyclics.
FROM ASH 2022
ITP: Biologic beat placebo, but few patients improved
NEW ORLEANS –
Nevertheless, “efgartigimod demonstrated a strong clinical benefit,” said hematologist/oncologist and study lead author Catherine M. Broome, MD, of Georgetown University, Washington, in an interview about the findings presented at the annual meeting of the American Society of Hematology.
“The data showed statistically significant and clinically meaningful improvement in platelet counts over placebo, a fast and robust platelet count improvement over placebo, and the confirmed ability for every-other-week dosing, as well as a favorable safety and tolerability profile, consistent with previous clinical trials,” she said.
In ITP, according to the National Organization for Rare Disorders, “the patient’s immune system tags their own platelets as ‘foreign,’ leading their B lymphocytes and plasma cells to produce self-reactive antiplatelet antibodies that attach to platelet surface.”
The prevalence of ITP among adults in the United States is 9.5 per 100,000, NORD says. Children are also affected, but they usually recover. An estimated 60% of adults recover within 3 years.
Treatment options include corticosteroids and intravenous immunoglobulin.
“There are a relatively large number of current treatments, and they tend to work well for most patients. However, there are a minority of patients who do not respond to or tolerate current therapies and would benefit from new treatment options,” said hematologist Adam C. Cuker, MD, MS, of Penn Medicine, Philadelphia, in an interview. He is chair of ASH’s Committee on Quality.
For the new industry-funded ADVANCE study, researchers recruited patients with long-standing, persistent/chronic ITP (an average of two platelet counts of < 30×109/L).
Subjects were randomized 2:1 to receive 10 mg/kg of efgartigimod weekly – or response-dependent doses after the first 4 weeks – or placebo for 24 weeks. There were 86 patients in the intervention group and 45 in the placebo group. Overall, 60 were male and 71 were female; 107 were under 65; 121 were White and 8 were Asian. Details about the others were not provided.
Subjects were allowed to take several other drugs such as oral corticosteroids, and oral thrombopoietin receptor agonists other than romiplostim.
Per the primary endpoint, 17/78 (21.8%) reached a sustained response, defined as platelet counts ≥ 50×109/L in ≥ four of six visits between weeks 19 and 24 without intercurrent events, such as rescue therapy at week 12 or later. In the placebo group, 2/40 reached this response (5.0%; P = .0316).
“The primary endpoint was a high bar to achieve,” Dr. Broome said. “This was a difficult-to-treat patient population heavily pretreated and refractory to other treatments: 68.6% of patients in the efgartigimod arm had received three or more prior ITP treatments.”
She added that “subgroup analyses – including prior ITP therapy, time since diagnosis, baseline platelet count and age/region demographics – of patients who achieved the primary endpoint all favored efgartigimod over placebo.”
Side effects were extremely common among both the drug and placebo groups, and serious adverse events were common in the placebo group. No deaths were reported.
Efgartigimod, a neonatal Fc receptor blocker, is an extremely expensive drug that is Food and Drug Administration approved for some cases of generalized myasthenia gravis. According to a report in Neurology earlier this year, company statements listed its price as $855,400 a year; the report questioned its cost-effectiveness.
In response to a query about price, Luc Truyen, MD, PhD, chief medical officer of drug manufacturer Argenx, declined to talk about cost – a sensitive topic for pharmaceutical companies. “It is too early to discuss pricing and access as no regulatory submission or discussion has occurred,” Dr. Truyen said.
Penn Medicine’s Dr. Cuker, who is familiar with the study findings, said the primary endpoint results are not very impressive. “That said, it should be borne in mind that the patients enrolled in the trial tended to be heavily pretreated and refractory patients,” he said.
As for adverse effects, he said the drug “appears to be safe and well tolerated. The biggest theoretical concern with this class of drugs is an increased risk of infection due to lowering of IgG levels.”
It would be helpful to have trials that directly compare second-line therapies in ITP, he added. “Unfortunately, no such trials exist, and pharmaceutical companies would not be motivated to conduct them.”
For now, he said, off-label use of efgartigimod “may be reasonable, but only in rare situations where other approved and better established ITP treatments have been exhausted.”
What’s next? According to Dr. Broome, another trial is currently evaluating efgartigimod for the treatment of primary ITP, with top-line data expected in the second half of 2023.
The study was funded by Argenx. Dr. Broome discloses honoraria from Alexion, Argenx, Apellis, and Sano. Dr. Truyen’s disclosures weren’t available. Dr. Cuker has no disclosures.
NEW ORLEANS –
Nevertheless, “efgartigimod demonstrated a strong clinical benefit,” said hematologist/oncologist and study lead author Catherine M. Broome, MD, of Georgetown University, Washington, in an interview about the findings presented at the annual meeting of the American Society of Hematology.
“The data showed statistically significant and clinically meaningful improvement in platelet counts over placebo, a fast and robust platelet count improvement over placebo, and the confirmed ability for every-other-week dosing, as well as a favorable safety and tolerability profile, consistent with previous clinical trials,” she said.
In ITP, according to the National Organization for Rare Disorders, “the patient’s immune system tags their own platelets as ‘foreign,’ leading their B lymphocytes and plasma cells to produce self-reactive antiplatelet antibodies that attach to platelet surface.”
The prevalence of ITP among adults in the United States is 9.5 per 100,000, NORD says. Children are also affected, but they usually recover. An estimated 60% of adults recover within 3 years.
Treatment options include corticosteroids and intravenous immunoglobulin.
“There are a relatively large number of current treatments, and they tend to work well for most patients. However, there are a minority of patients who do not respond to or tolerate current therapies and would benefit from new treatment options,” said hematologist Adam C. Cuker, MD, MS, of Penn Medicine, Philadelphia, in an interview. He is chair of ASH’s Committee on Quality.
For the new industry-funded ADVANCE study, researchers recruited patients with long-standing, persistent/chronic ITP (an average of two platelet counts of < 30×109/L).
Subjects were randomized 2:1 to receive 10 mg/kg of efgartigimod weekly – or response-dependent doses after the first 4 weeks – or placebo for 24 weeks. There were 86 patients in the intervention group and 45 in the placebo group. Overall, 60 were male and 71 were female; 107 were under 65; 121 were White and 8 were Asian. Details about the others were not provided.
Subjects were allowed to take several other drugs such as oral corticosteroids, and oral thrombopoietin receptor agonists other than romiplostim.
Per the primary endpoint, 17/78 (21.8%) reached a sustained response, defined as platelet counts ≥ 50×109/L in ≥ four of six visits between weeks 19 and 24 without intercurrent events, such as rescue therapy at week 12 or later. In the placebo group, 2/40 reached this response (5.0%; P = .0316).
“The primary endpoint was a high bar to achieve,” Dr. Broome said. “This was a difficult-to-treat patient population heavily pretreated and refractory to other treatments: 68.6% of patients in the efgartigimod arm had received three or more prior ITP treatments.”
She added that “subgroup analyses – including prior ITP therapy, time since diagnosis, baseline platelet count and age/region demographics – of patients who achieved the primary endpoint all favored efgartigimod over placebo.”
Side effects were extremely common among both the drug and placebo groups, and serious adverse events were common in the placebo group. No deaths were reported.
Efgartigimod, a neonatal Fc receptor blocker, is an extremely expensive drug that is Food and Drug Administration approved for some cases of generalized myasthenia gravis. According to a report in Neurology earlier this year, company statements listed its price as $855,400 a year; the report questioned its cost-effectiveness.
In response to a query about price, Luc Truyen, MD, PhD, chief medical officer of drug manufacturer Argenx, declined to talk about cost – a sensitive topic for pharmaceutical companies. “It is too early to discuss pricing and access as no regulatory submission or discussion has occurred,” Dr. Truyen said.
Penn Medicine’s Dr. Cuker, who is familiar with the study findings, said the primary endpoint results are not very impressive. “That said, it should be borne in mind that the patients enrolled in the trial tended to be heavily pretreated and refractory patients,” he said.
As for adverse effects, he said the drug “appears to be safe and well tolerated. The biggest theoretical concern with this class of drugs is an increased risk of infection due to lowering of IgG levels.”
It would be helpful to have trials that directly compare second-line therapies in ITP, he added. “Unfortunately, no such trials exist, and pharmaceutical companies would not be motivated to conduct them.”
For now, he said, off-label use of efgartigimod “may be reasonable, but only in rare situations where other approved and better established ITP treatments have been exhausted.”
What’s next? According to Dr. Broome, another trial is currently evaluating efgartigimod for the treatment of primary ITP, with top-line data expected in the second half of 2023.
The study was funded by Argenx. Dr. Broome discloses honoraria from Alexion, Argenx, Apellis, and Sano. Dr. Truyen’s disclosures weren’t available. Dr. Cuker has no disclosures.
NEW ORLEANS –
Nevertheless, “efgartigimod demonstrated a strong clinical benefit,” said hematologist/oncologist and study lead author Catherine M. Broome, MD, of Georgetown University, Washington, in an interview about the findings presented at the annual meeting of the American Society of Hematology.
“The data showed statistically significant and clinically meaningful improvement in platelet counts over placebo, a fast and robust platelet count improvement over placebo, and the confirmed ability for every-other-week dosing, as well as a favorable safety and tolerability profile, consistent with previous clinical trials,” she said.
In ITP, according to the National Organization for Rare Disorders, “the patient’s immune system tags their own platelets as ‘foreign,’ leading their B lymphocytes and plasma cells to produce self-reactive antiplatelet antibodies that attach to platelet surface.”
The prevalence of ITP among adults in the United States is 9.5 per 100,000, NORD says. Children are also affected, but they usually recover. An estimated 60% of adults recover within 3 years.
Treatment options include corticosteroids and intravenous immunoglobulin.
“There are a relatively large number of current treatments, and they tend to work well for most patients. However, there are a minority of patients who do not respond to or tolerate current therapies and would benefit from new treatment options,” said hematologist Adam C. Cuker, MD, MS, of Penn Medicine, Philadelphia, in an interview. He is chair of ASH’s Committee on Quality.
For the new industry-funded ADVANCE study, researchers recruited patients with long-standing, persistent/chronic ITP (an average of two platelet counts of < 30×109/L).
Subjects were randomized 2:1 to receive 10 mg/kg of efgartigimod weekly – or response-dependent doses after the first 4 weeks – or placebo for 24 weeks. There were 86 patients in the intervention group and 45 in the placebo group. Overall, 60 were male and 71 were female; 107 were under 65; 121 were White and 8 were Asian. Details about the others were not provided.
Subjects were allowed to take several other drugs such as oral corticosteroids, and oral thrombopoietin receptor agonists other than romiplostim.
Per the primary endpoint, 17/78 (21.8%) reached a sustained response, defined as platelet counts ≥ 50×109/L in ≥ four of six visits between weeks 19 and 24 without intercurrent events, such as rescue therapy at week 12 or later. In the placebo group, 2/40 reached this response (5.0%; P = .0316).
“The primary endpoint was a high bar to achieve,” Dr. Broome said. “This was a difficult-to-treat patient population heavily pretreated and refractory to other treatments: 68.6% of patients in the efgartigimod arm had received three or more prior ITP treatments.”
She added that “subgroup analyses – including prior ITP therapy, time since diagnosis, baseline platelet count and age/region demographics – of patients who achieved the primary endpoint all favored efgartigimod over placebo.”
Side effects were extremely common among both the drug and placebo groups, and serious adverse events were common in the placebo group. No deaths were reported.
Efgartigimod, a neonatal Fc receptor blocker, is an extremely expensive drug that is Food and Drug Administration approved for some cases of generalized myasthenia gravis. According to a report in Neurology earlier this year, company statements listed its price as $855,400 a year; the report questioned its cost-effectiveness.
In response to a query about price, Luc Truyen, MD, PhD, chief medical officer of drug manufacturer Argenx, declined to talk about cost – a sensitive topic for pharmaceutical companies. “It is too early to discuss pricing and access as no regulatory submission or discussion has occurred,” Dr. Truyen said.
Penn Medicine’s Dr. Cuker, who is familiar with the study findings, said the primary endpoint results are not very impressive. “That said, it should be borne in mind that the patients enrolled in the trial tended to be heavily pretreated and refractory patients,” he said.
As for adverse effects, he said the drug “appears to be safe and well tolerated. The biggest theoretical concern with this class of drugs is an increased risk of infection due to lowering of IgG levels.”
It would be helpful to have trials that directly compare second-line therapies in ITP, he added. “Unfortunately, no such trials exist, and pharmaceutical companies would not be motivated to conduct them.”
For now, he said, off-label use of efgartigimod “may be reasonable, but only in rare situations where other approved and better established ITP treatments have been exhausted.”
What’s next? According to Dr. Broome, another trial is currently evaluating efgartigimod for the treatment of primary ITP, with top-line data expected in the second half of 2023.
The study was funded by Argenx. Dr. Broome discloses honoraria from Alexion, Argenx, Apellis, and Sano. Dr. Truyen’s disclosures weren’t available. Dr. Cuker has no disclosures.
AT ASH 2022
Steep cost of surviving childhood HL: Epigenetic aging
AT ASH 2022 NEW ORLEANS
The research findings emerged from a study of nearly 500 individuals in their late 30s, of whom 215 were adult survivors of pediatric Hodgkin lymphoma (HL) and 282 were community controls.
The results showed that HL survivors had a higher epigenetic age relative to their chronological age, compared with controls, translating into epigenetic age acceleration over chronological age equivalent to a mean of 7.7 years.
In addition, this accelerated epigenetic aging in HL survivors was accompanied by neurocognitive deficits, including declines in visual-motor processing, short-term memory, verbal learning and recall, and executive function.
“We found that biologic aging is associated with long-term neurocognitive impairment in Hodgkin lymphoma survivors,” commented lead author AnnaLynn M. Williams, PhD, of the Wilmot Cancer Institute at the University of Rochester (N.Y.) “Specifically, we see strong and consistent associations with memory impairment, which suggests that biologic aging is likely related to cognitive aging.”
Dr. Williams presented the findings at the annual meeting of the American Society of Hematology.
“Our hope is that this biomarker may help us identify those survivors most at risk for early-onset cognitive aging and might actually help us gauge a preclinical response to interventions, so that we can see efficacy sooner than some other endpoints,” she said in a media briefing prior to presenting the data.
“This is an area that is very near and dear to my heart,” commented ASH President Jane N. Winter, MD, from Northwestern University, Chicago.
“Pediatricians have been very much wedded to very intensive therapies and intend to incorporate radiation more frequently in their treatment strategies for children than we do in adults,” she said. In addition, “we are very much focused on the long-term consequences of mediastinal radiation causing breast cancer in adults who were treated as young adults or children for Hodgkin lymphoma, but now we’re shedding a light on the neurocognitive deficits, which I think are underappreciated.”
Such HL therapies may exert a significant long-term impact on a patient population “that we otherwise cure,” Dr. Winter commented, pointing to a study by investigators in Germany that showed high unemployment levels among adult survivors of childhood HL, compared with the general population.
Also reacting to Dr. Williams’ findings, Catherine Bollard, MD, of the Center for Cancer and Immunology Research at Children’s National Research Institute in Washington, D.C., said: “My concern actually is that even today, in pediatrics, we’re still giving combined chemotherapy and radiation to the majority of the children with the more advanced disease, and that is not what is happening for the treatment of adult Hodgkin disease.”
She noted that there are now many immune-based therapies available for Hodgkin lymphoma that could soon obviate the need for chemotherapy.
Long-term complications
Dr. Williams and colleagues had previously reported that, compared with their healthy siblings, long-term survivors of HL had significantly higher risk (P < .05 for all comparisons) of neurocognitive impairment, anxiety, depression, unemployment, and impaired physical/mental quality of life.
In the current study, they looked specifically at epigenetic aging, and asked all participants to complete a comprehensive neuropsychological battery of tests.
The 215 trial participants who were survivors of pediatric HL came from the St Jude Lifetime Cohort. The mean patient age was 39, and the survivors were an average of 25 years out from their initial diagnosis.
The mean age of the 282 community controls was 36 years. Both the cohort and the controls were all European ancestry.
All participants provided a blood sample. The investigators performed genome-wide methylation studies on DNA derived from peripheral blood mononuclear cells (PBMC), and used the data to calculate epigenetic age according to a biomarker called DNAm PhenoAge. Also known as “Levine’s Clock,” this epigenetic biomarker of aging for life span and health span was developed by Morgan E. Levine, PhD, and colleagues at the University of California, Los Angeles, and other centers.
Dr. Williams and her team determined epigenetic age acceleration by calculating the difference between epigenetic and chronological age, with a higher epigenetic accelerated age suggesting an older biological age relative to the patient’s actual age.
As noted above, they found that HL survivors had a significantly higher epigenetic accelerated age, compared with controls, equivalent to a mean difference of 7.7 years (P < .001).
More than 80% of the survivors had some degree of accelerated aging, compared with only 23% of controls.
HL survivors with higher degrees (second and third tertiles) of accelerated aging had significantly worse visual-motor processing speed compared with survivors in the first (lowest) tertile, with survivors in the second tertile performing on average 0.42 standard deviations worse (P = .005) and those in the third tertile performing 0.55 SD worse (P < .001).
In addition, relative to first tertile survivors, those in the second and third tertiles performed worse on short-term memory, with a decrease of –0.42 SD (P = .011) and 0.59 SD (P < .001), respectively.
HL survivors in the third tertile performed worse than those in the other tertiles on measures of verbal learning (P =.007) and long-term verbal recall (P = .005), and those in the second or third tertiles had an average decline of 0.4 SD, compared with those in first tertile on verbal fluency, a measure of executive function.
The declines in neurocognitive measures among survivors were relatively small but clinically significant, Dr. Williams said, and were likely to prove troublesome for patients.
Dr. Williams added that she and her colleagues are currently compiling data on a comparison of neurocognitive scores between cohort members and control, for future publication, “but I can say that, in the majority of measures that are reported on, survivors do worse.”
The investigators are planning expansion of DNA methylation profiling in the St. Jude Lifetime Cohort and will follow survivors prospectively to look for changes in epigenetic acceleration and how those changes might predict who is most at risk for neurocognitive decline.
The study was supported by grants from the National Cancer Institute. Dr. Williams, Dr. Winter, and Dr. Bollard all reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ASH 2022 NEW ORLEANS
The research findings emerged from a study of nearly 500 individuals in their late 30s, of whom 215 were adult survivors of pediatric Hodgkin lymphoma (HL) and 282 were community controls.
The results showed that HL survivors had a higher epigenetic age relative to their chronological age, compared with controls, translating into epigenetic age acceleration over chronological age equivalent to a mean of 7.7 years.
In addition, this accelerated epigenetic aging in HL survivors was accompanied by neurocognitive deficits, including declines in visual-motor processing, short-term memory, verbal learning and recall, and executive function.
“We found that biologic aging is associated with long-term neurocognitive impairment in Hodgkin lymphoma survivors,” commented lead author AnnaLynn M. Williams, PhD, of the Wilmot Cancer Institute at the University of Rochester (N.Y.) “Specifically, we see strong and consistent associations with memory impairment, which suggests that biologic aging is likely related to cognitive aging.”
Dr. Williams presented the findings at the annual meeting of the American Society of Hematology.
“Our hope is that this biomarker may help us identify those survivors most at risk for early-onset cognitive aging and might actually help us gauge a preclinical response to interventions, so that we can see efficacy sooner than some other endpoints,” she said in a media briefing prior to presenting the data.
“This is an area that is very near and dear to my heart,” commented ASH President Jane N. Winter, MD, from Northwestern University, Chicago.
“Pediatricians have been very much wedded to very intensive therapies and intend to incorporate radiation more frequently in their treatment strategies for children than we do in adults,” she said. In addition, “we are very much focused on the long-term consequences of mediastinal radiation causing breast cancer in adults who were treated as young adults or children for Hodgkin lymphoma, but now we’re shedding a light on the neurocognitive deficits, which I think are underappreciated.”
Such HL therapies may exert a significant long-term impact on a patient population “that we otherwise cure,” Dr. Winter commented, pointing to a study by investigators in Germany that showed high unemployment levels among adult survivors of childhood HL, compared with the general population.
Also reacting to Dr. Williams’ findings, Catherine Bollard, MD, of the Center for Cancer and Immunology Research at Children’s National Research Institute in Washington, D.C., said: “My concern actually is that even today, in pediatrics, we’re still giving combined chemotherapy and radiation to the majority of the children with the more advanced disease, and that is not what is happening for the treatment of adult Hodgkin disease.”
She noted that there are now many immune-based therapies available for Hodgkin lymphoma that could soon obviate the need for chemotherapy.
Long-term complications
Dr. Williams and colleagues had previously reported that, compared with their healthy siblings, long-term survivors of HL had significantly higher risk (P < .05 for all comparisons) of neurocognitive impairment, anxiety, depression, unemployment, and impaired physical/mental quality of life.
In the current study, they looked specifically at epigenetic aging, and asked all participants to complete a comprehensive neuropsychological battery of tests.
The 215 trial participants who were survivors of pediatric HL came from the St Jude Lifetime Cohort. The mean patient age was 39, and the survivors were an average of 25 years out from their initial diagnosis.
The mean age of the 282 community controls was 36 years. Both the cohort and the controls were all European ancestry.
All participants provided a blood sample. The investigators performed genome-wide methylation studies on DNA derived from peripheral blood mononuclear cells (PBMC), and used the data to calculate epigenetic age according to a biomarker called DNAm PhenoAge. Also known as “Levine’s Clock,” this epigenetic biomarker of aging for life span and health span was developed by Morgan E. Levine, PhD, and colleagues at the University of California, Los Angeles, and other centers.
Dr. Williams and her team determined epigenetic age acceleration by calculating the difference between epigenetic and chronological age, with a higher epigenetic accelerated age suggesting an older biological age relative to the patient’s actual age.
As noted above, they found that HL survivors had a significantly higher epigenetic accelerated age, compared with controls, equivalent to a mean difference of 7.7 years (P < .001).
More than 80% of the survivors had some degree of accelerated aging, compared with only 23% of controls.
HL survivors with higher degrees (second and third tertiles) of accelerated aging had significantly worse visual-motor processing speed compared with survivors in the first (lowest) tertile, with survivors in the second tertile performing on average 0.42 standard deviations worse (P = .005) and those in the third tertile performing 0.55 SD worse (P < .001).
In addition, relative to first tertile survivors, those in the second and third tertiles performed worse on short-term memory, with a decrease of –0.42 SD (P = .011) and 0.59 SD (P < .001), respectively.
HL survivors in the third tertile performed worse than those in the other tertiles on measures of verbal learning (P =.007) and long-term verbal recall (P = .005), and those in the second or third tertiles had an average decline of 0.4 SD, compared with those in first tertile on verbal fluency, a measure of executive function.
The declines in neurocognitive measures among survivors were relatively small but clinically significant, Dr. Williams said, and were likely to prove troublesome for patients.
Dr. Williams added that she and her colleagues are currently compiling data on a comparison of neurocognitive scores between cohort members and control, for future publication, “but I can say that, in the majority of measures that are reported on, survivors do worse.”
The investigators are planning expansion of DNA methylation profiling in the St. Jude Lifetime Cohort and will follow survivors prospectively to look for changes in epigenetic acceleration and how those changes might predict who is most at risk for neurocognitive decline.
The study was supported by grants from the National Cancer Institute. Dr. Williams, Dr. Winter, and Dr. Bollard all reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ASH 2022 NEW ORLEANS
The research findings emerged from a study of nearly 500 individuals in their late 30s, of whom 215 were adult survivors of pediatric Hodgkin lymphoma (HL) and 282 were community controls.
The results showed that HL survivors had a higher epigenetic age relative to their chronological age, compared with controls, translating into epigenetic age acceleration over chronological age equivalent to a mean of 7.7 years.
In addition, this accelerated epigenetic aging in HL survivors was accompanied by neurocognitive deficits, including declines in visual-motor processing, short-term memory, verbal learning and recall, and executive function.
“We found that biologic aging is associated with long-term neurocognitive impairment in Hodgkin lymphoma survivors,” commented lead author AnnaLynn M. Williams, PhD, of the Wilmot Cancer Institute at the University of Rochester (N.Y.) “Specifically, we see strong and consistent associations with memory impairment, which suggests that biologic aging is likely related to cognitive aging.”
Dr. Williams presented the findings at the annual meeting of the American Society of Hematology.
“Our hope is that this biomarker may help us identify those survivors most at risk for early-onset cognitive aging and might actually help us gauge a preclinical response to interventions, so that we can see efficacy sooner than some other endpoints,” she said in a media briefing prior to presenting the data.
“This is an area that is very near and dear to my heart,” commented ASH President Jane N. Winter, MD, from Northwestern University, Chicago.
“Pediatricians have been very much wedded to very intensive therapies and intend to incorporate radiation more frequently in their treatment strategies for children than we do in adults,” she said. In addition, “we are very much focused on the long-term consequences of mediastinal radiation causing breast cancer in adults who were treated as young adults or children for Hodgkin lymphoma, but now we’re shedding a light on the neurocognitive deficits, which I think are underappreciated.”
Such HL therapies may exert a significant long-term impact on a patient population “that we otherwise cure,” Dr. Winter commented, pointing to a study by investigators in Germany that showed high unemployment levels among adult survivors of childhood HL, compared with the general population.
Also reacting to Dr. Williams’ findings, Catherine Bollard, MD, of the Center for Cancer and Immunology Research at Children’s National Research Institute in Washington, D.C., said: “My concern actually is that even today, in pediatrics, we’re still giving combined chemotherapy and radiation to the majority of the children with the more advanced disease, and that is not what is happening for the treatment of adult Hodgkin disease.”
She noted that there are now many immune-based therapies available for Hodgkin lymphoma that could soon obviate the need for chemotherapy.
Long-term complications
Dr. Williams and colleagues had previously reported that, compared with their healthy siblings, long-term survivors of HL had significantly higher risk (P < .05 for all comparisons) of neurocognitive impairment, anxiety, depression, unemployment, and impaired physical/mental quality of life.
In the current study, they looked specifically at epigenetic aging, and asked all participants to complete a comprehensive neuropsychological battery of tests.
The 215 trial participants who were survivors of pediatric HL came from the St Jude Lifetime Cohort. The mean patient age was 39, and the survivors were an average of 25 years out from their initial diagnosis.
The mean age of the 282 community controls was 36 years. Both the cohort and the controls were all European ancestry.
All participants provided a blood sample. The investigators performed genome-wide methylation studies on DNA derived from peripheral blood mononuclear cells (PBMC), and used the data to calculate epigenetic age according to a biomarker called DNAm PhenoAge. Also known as “Levine’s Clock,” this epigenetic biomarker of aging for life span and health span was developed by Morgan E. Levine, PhD, and colleagues at the University of California, Los Angeles, and other centers.
Dr. Williams and her team determined epigenetic age acceleration by calculating the difference between epigenetic and chronological age, with a higher epigenetic accelerated age suggesting an older biological age relative to the patient’s actual age.
As noted above, they found that HL survivors had a significantly higher epigenetic accelerated age, compared with controls, equivalent to a mean difference of 7.7 years (P < .001).
More than 80% of the survivors had some degree of accelerated aging, compared with only 23% of controls.
HL survivors with higher degrees (second and third tertiles) of accelerated aging had significantly worse visual-motor processing speed compared with survivors in the first (lowest) tertile, with survivors in the second tertile performing on average 0.42 standard deviations worse (P = .005) and those in the third tertile performing 0.55 SD worse (P < .001).
In addition, relative to first tertile survivors, those in the second and third tertiles performed worse on short-term memory, with a decrease of –0.42 SD (P = .011) and 0.59 SD (P < .001), respectively.
HL survivors in the third tertile performed worse than those in the other tertiles on measures of verbal learning (P =.007) and long-term verbal recall (P = .005), and those in the second or third tertiles had an average decline of 0.4 SD, compared with those in first tertile on verbal fluency, a measure of executive function.
The declines in neurocognitive measures among survivors were relatively small but clinically significant, Dr. Williams said, and were likely to prove troublesome for patients.
Dr. Williams added that she and her colleagues are currently compiling data on a comparison of neurocognitive scores between cohort members and control, for future publication, “but I can say that, in the majority of measures that are reported on, survivors do worse.”
The investigators are planning expansion of DNA methylation profiling in the St. Jude Lifetime Cohort and will follow survivors prospectively to look for changes in epigenetic acceleration and how those changes might predict who is most at risk for neurocognitive decline.
The study was supported by grants from the National Cancer Institute. Dr. Williams, Dr. Winter, and Dr. Bollard all reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Alloantibody registry would save lives, money
NEW ORLEANS – Save lives; save money. What’s not to love? That’s the claim made for a proposed nationwide data bank on alloantibodies, which develop in response to foreign red blood cells in individuals who undergo repeated blood transfusions. They can occur after pregnancy or transplants, as well as in patients with sickle cell disease.
“The findings from our model are pretty definitive,” said George Goshua, MD, MSc, of Yale University, New Haven, Conn. “Despite very conservative assumptions, our results still show a huge financial benefit to having a system in place to serve as a preventive net that catches patients before they have to go through a delayed hemolytic transfusion reaction (DHTR).”
Dr. Goshua presented the study at the American Society of Hematology annual meeting. The proposed registry would significantly reduce the risk that transfusion-dependent patients, and others who require occasional transfusions, would develop complications requiring hospitalization, he said.
A similar registry has been up and running in the Netherlands for 15 years, he said at a press briefing.
Briefing moderator Catherine Bollard, MD, of the Center for Cancer and Immunology at Children’s National Research Institute in Washington, asked Dr. Goshua why such an exchange hasn’t been started in the United States already.
“I will say first that our European colleagues are far ahead in terms of preventative care,” he replied.
“On top of that, there’s a unique environment in the United States – and this dates back about 15 years now – where we are almost allergic to putting costs on benefits, that is, attaching a cost value to a benefit that a population can gain,” Dr. Goshua said. “So in this context, there hasn’t been an analysis that shows that this [exchange] actually makes sense, but I think it’s one of those analyses kind of showing people that the sky is blue but proving it quantitatively.”
Dr. Bollard said that the potential beneficial impact of such an exchange “is huge,” but it would “require upfront expenditure to actually realize these massive gains you will get down the road for these patients.”
Would be cost-effective
Although hospitals and transfusion centers check donated blood against an individual patient’s alloantibody profile, that information is usually kept in localized records and is not typically shared across health systems nationwide.
It’s different in the Netherlands, where the Transfusion Register of Irregular Antibodies and Cross-match Problems (TRIX) was launched in 2007. Under this system, transfusion laboratories register the presence of irregular red blood cell alloantibodies for their patients and can consult the database for information that is relevant for pretransfusion testing.
To see whether such a system, if implemented in the United States, would satisfy even the most parsimonious administrator or insurer, Dr. Goshua and colleagues created a computer simulation.
They estimated age- and gender-adjusted quality-adjusted life years (QALYs) for patients living with sickle cell disease, who typically require frequent transfusions and are thus especially at risk for developing alloantibodies and immune reactions from repeat exposures to the blood of others.
The model included age- and gender-adjusted costs based on 10 years of claims data, with the assumption that equal numbers of male and females would be in the sample.
The model estimated that by reducing DHTR incidence and DHTR-specific mortality in 20% to 44% of alloimmunized patients (a very conservative estimate, according to Dr. Goshua), the existence of a U.S. exchange would result in a gain of between 7,140 and 15,710 QALYs.
Assuming a willingness to pay up to $100,000 per QALY, a commonly used threshold in economic analyses in the United States, the exchange (vs. no exchange) would be preferred in 100% of 10,000 different iterations of a cost-effectiveness acceptability curve, Dr. Goshua said.
Even if the lifetime operational costs of such an exchange exceeded $600 million, it would still be cost-effective, and the net monetary benefit to the U.S. economy would be $0.7 billion, the authors found.
And although the model was limited to patients with sickle cell anemia, many other alloimmunized patients would be likely to benefit from such an exchange, including women with a prior pregnancy, and patients with autoimmunity, myelodysplastic syndrome, or beta-thalassemia, Dr. Goshua said.
The study was supported by the American Society of Hematology, the Yale School of Medicine, and Yale Center. Dr. Goshua and Dr. Bollard reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
NEW ORLEANS – Save lives; save money. What’s not to love? That’s the claim made for a proposed nationwide data bank on alloantibodies, which develop in response to foreign red blood cells in individuals who undergo repeated blood transfusions. They can occur after pregnancy or transplants, as well as in patients with sickle cell disease.
“The findings from our model are pretty definitive,” said George Goshua, MD, MSc, of Yale University, New Haven, Conn. “Despite very conservative assumptions, our results still show a huge financial benefit to having a system in place to serve as a preventive net that catches patients before they have to go through a delayed hemolytic transfusion reaction (DHTR).”
Dr. Goshua presented the study at the American Society of Hematology annual meeting. The proposed registry would significantly reduce the risk that transfusion-dependent patients, and others who require occasional transfusions, would develop complications requiring hospitalization, he said.
A similar registry has been up and running in the Netherlands for 15 years, he said at a press briefing.
Briefing moderator Catherine Bollard, MD, of the Center for Cancer and Immunology at Children’s National Research Institute in Washington, asked Dr. Goshua why such an exchange hasn’t been started in the United States already.
“I will say first that our European colleagues are far ahead in terms of preventative care,” he replied.
“On top of that, there’s a unique environment in the United States – and this dates back about 15 years now – where we are almost allergic to putting costs on benefits, that is, attaching a cost value to a benefit that a population can gain,” Dr. Goshua said. “So in this context, there hasn’t been an analysis that shows that this [exchange] actually makes sense, but I think it’s one of those analyses kind of showing people that the sky is blue but proving it quantitatively.”
Dr. Bollard said that the potential beneficial impact of such an exchange “is huge,” but it would “require upfront expenditure to actually realize these massive gains you will get down the road for these patients.”
Would be cost-effective
Although hospitals and transfusion centers check donated blood against an individual patient’s alloantibody profile, that information is usually kept in localized records and is not typically shared across health systems nationwide.
It’s different in the Netherlands, where the Transfusion Register of Irregular Antibodies and Cross-match Problems (TRIX) was launched in 2007. Under this system, transfusion laboratories register the presence of irregular red blood cell alloantibodies for their patients and can consult the database for information that is relevant for pretransfusion testing.
To see whether such a system, if implemented in the United States, would satisfy even the most parsimonious administrator or insurer, Dr. Goshua and colleagues created a computer simulation.
They estimated age- and gender-adjusted quality-adjusted life years (QALYs) for patients living with sickle cell disease, who typically require frequent transfusions and are thus especially at risk for developing alloantibodies and immune reactions from repeat exposures to the blood of others.
The model included age- and gender-adjusted costs based on 10 years of claims data, with the assumption that equal numbers of male and females would be in the sample.
The model estimated that by reducing DHTR incidence and DHTR-specific mortality in 20% to 44% of alloimmunized patients (a very conservative estimate, according to Dr. Goshua), the existence of a U.S. exchange would result in a gain of between 7,140 and 15,710 QALYs.
Assuming a willingness to pay up to $100,000 per QALY, a commonly used threshold in economic analyses in the United States, the exchange (vs. no exchange) would be preferred in 100% of 10,000 different iterations of a cost-effectiveness acceptability curve, Dr. Goshua said.
Even if the lifetime operational costs of such an exchange exceeded $600 million, it would still be cost-effective, and the net monetary benefit to the U.S. economy would be $0.7 billion, the authors found.
And although the model was limited to patients with sickle cell anemia, many other alloimmunized patients would be likely to benefit from such an exchange, including women with a prior pregnancy, and patients with autoimmunity, myelodysplastic syndrome, or beta-thalassemia, Dr. Goshua said.
The study was supported by the American Society of Hematology, the Yale School of Medicine, and Yale Center. Dr. Goshua and Dr. Bollard reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
NEW ORLEANS – Save lives; save money. What’s not to love? That’s the claim made for a proposed nationwide data bank on alloantibodies, which develop in response to foreign red blood cells in individuals who undergo repeated blood transfusions. They can occur after pregnancy or transplants, as well as in patients with sickle cell disease.
“The findings from our model are pretty definitive,” said George Goshua, MD, MSc, of Yale University, New Haven, Conn. “Despite very conservative assumptions, our results still show a huge financial benefit to having a system in place to serve as a preventive net that catches patients before they have to go through a delayed hemolytic transfusion reaction (DHTR).”
Dr. Goshua presented the study at the American Society of Hematology annual meeting. The proposed registry would significantly reduce the risk that transfusion-dependent patients, and others who require occasional transfusions, would develop complications requiring hospitalization, he said.
A similar registry has been up and running in the Netherlands for 15 years, he said at a press briefing.
Briefing moderator Catherine Bollard, MD, of the Center for Cancer and Immunology at Children’s National Research Institute in Washington, asked Dr. Goshua why such an exchange hasn’t been started in the United States already.
“I will say first that our European colleagues are far ahead in terms of preventative care,” he replied.
“On top of that, there’s a unique environment in the United States – and this dates back about 15 years now – where we are almost allergic to putting costs on benefits, that is, attaching a cost value to a benefit that a population can gain,” Dr. Goshua said. “So in this context, there hasn’t been an analysis that shows that this [exchange] actually makes sense, but I think it’s one of those analyses kind of showing people that the sky is blue but proving it quantitatively.”
Dr. Bollard said that the potential beneficial impact of such an exchange “is huge,” but it would “require upfront expenditure to actually realize these massive gains you will get down the road for these patients.”
Would be cost-effective
Although hospitals and transfusion centers check donated blood against an individual patient’s alloantibody profile, that information is usually kept in localized records and is not typically shared across health systems nationwide.
It’s different in the Netherlands, where the Transfusion Register of Irregular Antibodies and Cross-match Problems (TRIX) was launched in 2007. Under this system, transfusion laboratories register the presence of irregular red blood cell alloantibodies for their patients and can consult the database for information that is relevant for pretransfusion testing.
To see whether such a system, if implemented in the United States, would satisfy even the most parsimonious administrator or insurer, Dr. Goshua and colleagues created a computer simulation.
They estimated age- and gender-adjusted quality-adjusted life years (QALYs) for patients living with sickle cell disease, who typically require frequent transfusions and are thus especially at risk for developing alloantibodies and immune reactions from repeat exposures to the blood of others.
The model included age- and gender-adjusted costs based on 10 years of claims data, with the assumption that equal numbers of male and females would be in the sample.
The model estimated that by reducing DHTR incidence and DHTR-specific mortality in 20% to 44% of alloimmunized patients (a very conservative estimate, according to Dr. Goshua), the existence of a U.S. exchange would result in a gain of between 7,140 and 15,710 QALYs.
Assuming a willingness to pay up to $100,000 per QALY, a commonly used threshold in economic analyses in the United States, the exchange (vs. no exchange) would be preferred in 100% of 10,000 different iterations of a cost-effectiveness acceptability curve, Dr. Goshua said.
Even if the lifetime operational costs of such an exchange exceeded $600 million, it would still be cost-effective, and the net monetary benefit to the U.S. economy would be $0.7 billion, the authors found.
And although the model was limited to patients with sickle cell anemia, many other alloimmunized patients would be likely to benefit from such an exchange, including women with a prior pregnancy, and patients with autoimmunity, myelodysplastic syndrome, or beta-thalassemia, Dr. Goshua said.
The study was supported by the American Society of Hematology, the Yale School of Medicine, and Yale Center. Dr. Goshua and Dr. Bollard reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ASH 2022
Beta-thalassemia: Benefits of gene therapy outweigh costs
Surveyed at 3 years, patients also reported ongoing benefits from treatment, including positive impacts on employment, school attendance, and physical activity, according to a second report.
The findings address a major question about betibeglogene autotemcel: Its durability. The therapy is priced at over $2 million per treatment, based on the premise that it will benefit patients in the long-term, in part by offsetting the cost of ongoing transfusions. Therefore, proof of long-standing benefit is important.
The Food and Drug Administration approved betibeglogene autotemcel in August 2022 for children and adults with transfusion dependent beta-thalassemia, a condition that causes patients to have absent or reduced levels of hemoglobin due to mutations in the beta-globin gene. Patients typically require transfusions every 2-5 weeks.
The treatment inserts functional copies of the mutated gene into the patients’ hematopoietic stem cells via a replication-defective lentivirus. The cells are then transfused back into the patient.
As of August 2021, 63 patients had undergone treatment and been followed for a median of 41.4 months. So far, durability looks solid.
“We now have up to 8 years efficacy and safety follow-up” with beti-cel. “Patients experience durable transfusion independence,” said Mark Walters, MD, a pediatric hematologist/oncologist at the University of California, San Francisco, who presented the long-term efficacy data at the meeting.
Overall, 89.5% of patients (34/38) in phase 3 testing achieved transfusion independence, meaning that they had hemoglobin levels of at least 9 g/dL without transfusions for a year or more.
The response rate was an improvement over phase 1/2 testing, in which 68% of subjects (15/22) became transfusion free. Improvements in the manufacturing process led to better outcomes in phase 3, Dr. Walters said.
As for quality of life (QoL), improvement “continues through 3 years following treatment,” said Franco Locatelli, MD, a pediatric hematologist/oncologist at Catholic University of the Sacred Heart, Rome, who led the QoL study.
When patients who achieved transfusion independence were surveyed 3 years after treatment, 93% of adults were employed or able to seek employment, up from 67% before treatment. School absences were down among children, almost half of subjects no longer needed symptom management, and 81% reported improvements in physical activity.
There were also improvements on various quality of life scales, including in physical functioning and mental health.
Patient age and underlying thalassemia genotype had no impact on the likelihood of transfusion independence. Those who achieved it also had reductions in markers of ineffective erythropoiesis and iron overload.
On multivariate analysis, the greatest predictor of transfusion independence was having at least 62% of cells transduced prior to reintroduction to the patient.
As for adverse events, seven subjects (11%) developed severe veno-occlusive liver disease that resolved with supportive care. Mucositis and febrile neutropenia are also a concern and related to the busulfan conditioning regimen.
No malignancies, insertional oncogenesis, or lentivirus replication have been observed.
The studies were funded by beti-cel maker Bluebird Bio, and many of the investigators are employees. Others reported ties to Bluebird and a range of other companies. Among his industry ties, Dr. Locatelli is a speaker for Bluebird. Dr. Walters also had industry relationships, but didn’t report any ties to Bluebird.
Surveyed at 3 years, patients also reported ongoing benefits from treatment, including positive impacts on employment, school attendance, and physical activity, according to a second report.
The findings address a major question about betibeglogene autotemcel: Its durability. The therapy is priced at over $2 million per treatment, based on the premise that it will benefit patients in the long-term, in part by offsetting the cost of ongoing transfusions. Therefore, proof of long-standing benefit is important.
The Food and Drug Administration approved betibeglogene autotemcel in August 2022 for children and adults with transfusion dependent beta-thalassemia, a condition that causes patients to have absent or reduced levels of hemoglobin due to mutations in the beta-globin gene. Patients typically require transfusions every 2-5 weeks.
The treatment inserts functional copies of the mutated gene into the patients’ hematopoietic stem cells via a replication-defective lentivirus. The cells are then transfused back into the patient.
As of August 2021, 63 patients had undergone treatment and been followed for a median of 41.4 months. So far, durability looks solid.
“We now have up to 8 years efficacy and safety follow-up” with beti-cel. “Patients experience durable transfusion independence,” said Mark Walters, MD, a pediatric hematologist/oncologist at the University of California, San Francisco, who presented the long-term efficacy data at the meeting.
Overall, 89.5% of patients (34/38) in phase 3 testing achieved transfusion independence, meaning that they had hemoglobin levels of at least 9 g/dL without transfusions for a year or more.
The response rate was an improvement over phase 1/2 testing, in which 68% of subjects (15/22) became transfusion free. Improvements in the manufacturing process led to better outcomes in phase 3, Dr. Walters said.
As for quality of life (QoL), improvement “continues through 3 years following treatment,” said Franco Locatelli, MD, a pediatric hematologist/oncologist at Catholic University of the Sacred Heart, Rome, who led the QoL study.
When patients who achieved transfusion independence were surveyed 3 years after treatment, 93% of adults were employed or able to seek employment, up from 67% before treatment. School absences were down among children, almost half of subjects no longer needed symptom management, and 81% reported improvements in physical activity.
There were also improvements on various quality of life scales, including in physical functioning and mental health.
Patient age and underlying thalassemia genotype had no impact on the likelihood of transfusion independence. Those who achieved it also had reductions in markers of ineffective erythropoiesis and iron overload.
On multivariate analysis, the greatest predictor of transfusion independence was having at least 62% of cells transduced prior to reintroduction to the patient.
As for adverse events, seven subjects (11%) developed severe veno-occlusive liver disease that resolved with supportive care. Mucositis and febrile neutropenia are also a concern and related to the busulfan conditioning regimen.
No malignancies, insertional oncogenesis, or lentivirus replication have been observed.
The studies were funded by beti-cel maker Bluebird Bio, and many of the investigators are employees. Others reported ties to Bluebird and a range of other companies. Among his industry ties, Dr. Locatelli is a speaker for Bluebird. Dr. Walters also had industry relationships, but didn’t report any ties to Bluebird.
Surveyed at 3 years, patients also reported ongoing benefits from treatment, including positive impacts on employment, school attendance, and physical activity, according to a second report.
The findings address a major question about betibeglogene autotemcel: Its durability. The therapy is priced at over $2 million per treatment, based on the premise that it will benefit patients in the long-term, in part by offsetting the cost of ongoing transfusions. Therefore, proof of long-standing benefit is important.
The Food and Drug Administration approved betibeglogene autotemcel in August 2022 for children and adults with transfusion dependent beta-thalassemia, a condition that causes patients to have absent or reduced levels of hemoglobin due to mutations in the beta-globin gene. Patients typically require transfusions every 2-5 weeks.
The treatment inserts functional copies of the mutated gene into the patients’ hematopoietic stem cells via a replication-defective lentivirus. The cells are then transfused back into the patient.
As of August 2021, 63 patients had undergone treatment and been followed for a median of 41.4 months. So far, durability looks solid.
“We now have up to 8 years efficacy and safety follow-up” with beti-cel. “Patients experience durable transfusion independence,” said Mark Walters, MD, a pediatric hematologist/oncologist at the University of California, San Francisco, who presented the long-term efficacy data at the meeting.
Overall, 89.5% of patients (34/38) in phase 3 testing achieved transfusion independence, meaning that they had hemoglobin levels of at least 9 g/dL without transfusions for a year or more.
The response rate was an improvement over phase 1/2 testing, in which 68% of subjects (15/22) became transfusion free. Improvements in the manufacturing process led to better outcomes in phase 3, Dr. Walters said.
As for quality of life (QoL), improvement “continues through 3 years following treatment,” said Franco Locatelli, MD, a pediatric hematologist/oncologist at Catholic University of the Sacred Heart, Rome, who led the QoL study.
When patients who achieved transfusion independence were surveyed 3 years after treatment, 93% of adults were employed or able to seek employment, up from 67% before treatment. School absences were down among children, almost half of subjects no longer needed symptom management, and 81% reported improvements in physical activity.
There were also improvements on various quality of life scales, including in physical functioning and mental health.
Patient age and underlying thalassemia genotype had no impact on the likelihood of transfusion independence. Those who achieved it also had reductions in markers of ineffective erythropoiesis and iron overload.
On multivariate analysis, the greatest predictor of transfusion independence was having at least 62% of cells transduced prior to reintroduction to the patient.
As for adverse events, seven subjects (11%) developed severe veno-occlusive liver disease that resolved with supportive care. Mucositis and febrile neutropenia are also a concern and related to the busulfan conditioning regimen.
No malignancies, insertional oncogenesis, or lentivirus replication have been observed.
The studies were funded by beti-cel maker Bluebird Bio, and many of the investigators are employees. Others reported ties to Bluebird and a range of other companies. Among his industry ties, Dr. Locatelli is a speaker for Bluebird. Dr. Walters also had industry relationships, but didn’t report any ties to Bluebird.
FROM ASH 2022
‘Exciting’ responsiveness to talquetamab for r/r MM
“Talquetamab is a novel agent directed against a new antigen target in myeloma,” explained lead investigator Ajai Chari, MD, of Icahn School of Medicine at Mount Sinai in New York.
The product has demonstrated “a response rate of 73% to 74% with both weekly and every 2-week schedules in a heavily treated patient population. Even in those patients with prior T-cell redirection, we see a 63% response rate,” said Dr. Chari, who reported the data at the American Society of Hematology annual meeting.
It is encouraging to see high response rates among patients with disease that is refractory to multiple prior lines of therapy, and the results suggest that talquetamab may buy time for patients with few other options, said Stephanie Lee, MD, MPH, of the Fred Hutchinson Cancer Center in Seattle, and a former ASH president.
“It looks like there are responses even in people who are heavily pretreated and have had other agents similar to it, “ she said. “We hear about ‘penta-refractory’ [disease] and everything, and I think we’re going to start hearing about ‘octo-refractory’ and ‘deci-refractory,’ and those things. It’s really exciting [to see these responses],” she said. Dr. Lee moderated a media briefing prior to Dr. Chari’s discussion of the data.
Talquetamab is a bispecific antibody directed against a novel target with the prosaic name of “G protein–coupled receptor, family C, group 5, member D” or simply GPRC5D. The antigen is a so-called “orphan” receptor with an unidentified ligand. The receptor is expressed in malignant plasma cells, making it a particularly attractive target for the treatment of patients with multiple myeloma.
“It’s important to pick the right target for these [patients] and GPRC5D is a good candidate for that because it’s highly expressed on myeloma cells but spares normal tissues, in particular the hematopoietic stem cells for the precursors to their blood,” Dr. Chari said.
The new drug could be available next year. The manufacturer, Janssen, announced last week that it had submitted an approval application with the Food and Drug Administration for talquetamab use in the treatment of patients with relapsed or refractory multiple myeloma.
The clinical results so far “indicate the potential of this treatment for heavily pretreated patients who have exhausted currently approved therapies,” Dr. Chari said in a statement.
MonumenTAL study
Dr. Chari and colleagues recently reported results of the phase 1 MonumenTAL-1 study in The New England Journal of Medicine. At ASH 2022, they reported phase 2 results from the same study, including some patients carried over from phase 1, but also a subgroup of patients with prior exposure to either chimeric antigen receptor T-cell (CAR-T) therapy or other bispecific T cell-engaging antibodies.
In the phase 1 dose-escalation study published in NEJM, the response rates among patients who had a median of six prior lines of therapy ranged from 64% to 70%. The drug was delivered in this phase at a variety of dose levels and schedules, and both intravenously and subcutaneously.
Three cohorts, two doses
The phase 2 study enrolled patients who had a minimum of three prior lines of therapy including a proteasome inhibitor, immunomodulating agent, and anti-CD38 antibody, and who had good-to-fair performance status.
There were three cohorts. The first cohort comprised 21 patients from phase 1 and 122 from phase 2 who received talquetamab at a dose of 0.4 mg/kg subcutaneously once weekly. These patients were allowed to have received prior therapy with an antibody-drug conjugate (ADC) targeted against B-cell maturation antigen (BCMA), but could not have received a prior T-cell redirection therapy.
The second cohort comprised 36 patients in phase 1 and 109 in phase 2 who were treated with 0.8 mg/kg subcutaneously every 2 weeks. These patients had the same prior therapy allowances and restrictions as the first cohort.
The third cohort comprised 17 patients in phase 1 plus 34 patients in phase 2 who had received either CAR T-cell receptor therapy or a different bispecific T-cell engager. These patients received either 0.4 mg/kg weekly subcutaneous talquetamab, or 0.8 mg/kg every 2 weeks.
Phase 2 results
The overall response rate (ORR) among patients treated at 0.4 mg/kg weekly was 74.1%, including 23.8% stringent complete responses (sCR), 9.8% complete response (CR), 25.9% very good partial responses (VGPR) and 14.7% partial responses (PR).
The ORR among patients treated at the 0.8 mg/kg every 2 week dose was 73.1%, consisting of 20% sCR, 12.4% CR, 24,8% VGPR, and 15.9% PR.
The response rates were consistent across subgroups, including baseline International Staging System (ISS) stage III disease, baseline cytogenetic risk, number of prior therapies, degree of refractoriness to prior therapy, and prior exposure to the anti-BCMA antibody belantamab (except patients with baseline plasmacytomas).
The median durations of responses were 9.3 months and 13 months in the 0.4 and 0.8 mg/kg doses, respectively. The median duration of response was not reached among patients who had achieved a CR or better in either dosing group.
Safety profile
Most adverse events of grade 3 or 4 were cytopenias, including anemia, neutropenia, lymphopenia, and thrombocytopenia. These adverse events were generally limited to the first three cycles, and less than a third of all cytopenias were grade 3 or greater.
Infection occurred in 57.3% of patients treated at 0.4 mg/kg weekly and 50.3% treated at 0.8 mg/kg every 2 weeks. Of these infections, 16.8% and 11.7%, respectively, were grade 3 or 4.
Opportunistic infections were seen in 3.5% of patients treated at 0.4 mg/kg and 2.8% of those treated at 0.8 mg/kg.
Taste alterations (dysgeusia) occurred in nearly half of patients in each dosing group. Dysgeusia was managed with supportive care, including hydration, and in some cases with dose reductions.
Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 10% to 11% of patients, but most of these events were grade 1 or 2.
What’s next?
At the briefing, this news organization asked Dr. Chari whether, given the evident efficacy and relative safety of this agent, it could be moved up higher in the therapeutic lines and combined with other agents such as proteasome inhibitors (bortezomib et al.), immunomodulators (lenalidomide and others) and CD38-directed antibodies (daratumumab, etc.)
Dr. Chari replied that several studies combining talquetamab with agents in all of these classes and with other bispecific T-cell engagers are currently underway.
Dr. Chari disclosed consulting fees from Janssen, which supported the study. Dr. Lee has received clinical trial research funding from Amgen, AstraZeneca, Incyte, Kadmon, Novartis, Pfizer, Syndax, and Takeda and has served as a consultant to Incyte.
A version of this article first appeared on Medscape.com.
“Talquetamab is a novel agent directed against a new antigen target in myeloma,” explained lead investigator Ajai Chari, MD, of Icahn School of Medicine at Mount Sinai in New York.
The product has demonstrated “a response rate of 73% to 74% with both weekly and every 2-week schedules in a heavily treated patient population. Even in those patients with prior T-cell redirection, we see a 63% response rate,” said Dr. Chari, who reported the data at the American Society of Hematology annual meeting.
It is encouraging to see high response rates among patients with disease that is refractory to multiple prior lines of therapy, and the results suggest that talquetamab may buy time for patients with few other options, said Stephanie Lee, MD, MPH, of the Fred Hutchinson Cancer Center in Seattle, and a former ASH president.
“It looks like there are responses even in people who are heavily pretreated and have had other agents similar to it, “ she said. “We hear about ‘penta-refractory’ [disease] and everything, and I think we’re going to start hearing about ‘octo-refractory’ and ‘deci-refractory,’ and those things. It’s really exciting [to see these responses],” she said. Dr. Lee moderated a media briefing prior to Dr. Chari’s discussion of the data.
Talquetamab is a bispecific antibody directed against a novel target with the prosaic name of “G protein–coupled receptor, family C, group 5, member D” or simply GPRC5D. The antigen is a so-called “orphan” receptor with an unidentified ligand. The receptor is expressed in malignant plasma cells, making it a particularly attractive target for the treatment of patients with multiple myeloma.
“It’s important to pick the right target for these [patients] and GPRC5D is a good candidate for that because it’s highly expressed on myeloma cells but spares normal tissues, in particular the hematopoietic stem cells for the precursors to their blood,” Dr. Chari said.
The new drug could be available next year. The manufacturer, Janssen, announced last week that it had submitted an approval application with the Food and Drug Administration for talquetamab use in the treatment of patients with relapsed or refractory multiple myeloma.
The clinical results so far “indicate the potential of this treatment for heavily pretreated patients who have exhausted currently approved therapies,” Dr. Chari said in a statement.
MonumenTAL study
Dr. Chari and colleagues recently reported results of the phase 1 MonumenTAL-1 study in The New England Journal of Medicine. At ASH 2022, they reported phase 2 results from the same study, including some patients carried over from phase 1, but also a subgroup of patients with prior exposure to either chimeric antigen receptor T-cell (CAR-T) therapy or other bispecific T cell-engaging antibodies.
In the phase 1 dose-escalation study published in NEJM, the response rates among patients who had a median of six prior lines of therapy ranged from 64% to 70%. The drug was delivered in this phase at a variety of dose levels and schedules, and both intravenously and subcutaneously.
Three cohorts, two doses
The phase 2 study enrolled patients who had a minimum of three prior lines of therapy including a proteasome inhibitor, immunomodulating agent, and anti-CD38 antibody, and who had good-to-fair performance status.
There were three cohorts. The first cohort comprised 21 patients from phase 1 and 122 from phase 2 who received talquetamab at a dose of 0.4 mg/kg subcutaneously once weekly. These patients were allowed to have received prior therapy with an antibody-drug conjugate (ADC) targeted against B-cell maturation antigen (BCMA), but could not have received a prior T-cell redirection therapy.
The second cohort comprised 36 patients in phase 1 and 109 in phase 2 who were treated with 0.8 mg/kg subcutaneously every 2 weeks. These patients had the same prior therapy allowances and restrictions as the first cohort.
The third cohort comprised 17 patients in phase 1 plus 34 patients in phase 2 who had received either CAR T-cell receptor therapy or a different bispecific T-cell engager. These patients received either 0.4 mg/kg weekly subcutaneous talquetamab, or 0.8 mg/kg every 2 weeks.
Phase 2 results
The overall response rate (ORR) among patients treated at 0.4 mg/kg weekly was 74.1%, including 23.8% stringent complete responses (sCR), 9.8% complete response (CR), 25.9% very good partial responses (VGPR) and 14.7% partial responses (PR).
The ORR among patients treated at the 0.8 mg/kg every 2 week dose was 73.1%, consisting of 20% sCR, 12.4% CR, 24,8% VGPR, and 15.9% PR.
The response rates were consistent across subgroups, including baseline International Staging System (ISS) stage III disease, baseline cytogenetic risk, number of prior therapies, degree of refractoriness to prior therapy, and prior exposure to the anti-BCMA antibody belantamab (except patients with baseline plasmacytomas).
The median durations of responses were 9.3 months and 13 months in the 0.4 and 0.8 mg/kg doses, respectively. The median duration of response was not reached among patients who had achieved a CR or better in either dosing group.
Safety profile
Most adverse events of grade 3 or 4 were cytopenias, including anemia, neutropenia, lymphopenia, and thrombocytopenia. These adverse events were generally limited to the first three cycles, and less than a third of all cytopenias were grade 3 or greater.
Infection occurred in 57.3% of patients treated at 0.4 mg/kg weekly and 50.3% treated at 0.8 mg/kg every 2 weeks. Of these infections, 16.8% and 11.7%, respectively, were grade 3 or 4.
Opportunistic infections were seen in 3.5% of patients treated at 0.4 mg/kg and 2.8% of those treated at 0.8 mg/kg.
Taste alterations (dysgeusia) occurred in nearly half of patients in each dosing group. Dysgeusia was managed with supportive care, including hydration, and in some cases with dose reductions.
Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 10% to 11% of patients, but most of these events were grade 1 or 2.
What’s next?
At the briefing, this news organization asked Dr. Chari whether, given the evident efficacy and relative safety of this agent, it could be moved up higher in the therapeutic lines and combined with other agents such as proteasome inhibitors (bortezomib et al.), immunomodulators (lenalidomide and others) and CD38-directed antibodies (daratumumab, etc.)
Dr. Chari replied that several studies combining talquetamab with agents in all of these classes and with other bispecific T-cell engagers are currently underway.
Dr. Chari disclosed consulting fees from Janssen, which supported the study. Dr. Lee has received clinical trial research funding from Amgen, AstraZeneca, Incyte, Kadmon, Novartis, Pfizer, Syndax, and Takeda and has served as a consultant to Incyte.
A version of this article first appeared on Medscape.com.
“Talquetamab is a novel agent directed against a new antigen target in myeloma,” explained lead investigator Ajai Chari, MD, of Icahn School of Medicine at Mount Sinai in New York.
The product has demonstrated “a response rate of 73% to 74% with both weekly and every 2-week schedules in a heavily treated patient population. Even in those patients with prior T-cell redirection, we see a 63% response rate,” said Dr. Chari, who reported the data at the American Society of Hematology annual meeting.
It is encouraging to see high response rates among patients with disease that is refractory to multiple prior lines of therapy, and the results suggest that talquetamab may buy time for patients with few other options, said Stephanie Lee, MD, MPH, of the Fred Hutchinson Cancer Center in Seattle, and a former ASH president.
“It looks like there are responses even in people who are heavily pretreated and have had other agents similar to it, “ she said. “We hear about ‘penta-refractory’ [disease] and everything, and I think we’re going to start hearing about ‘octo-refractory’ and ‘deci-refractory,’ and those things. It’s really exciting [to see these responses],” she said. Dr. Lee moderated a media briefing prior to Dr. Chari’s discussion of the data.
Talquetamab is a bispecific antibody directed against a novel target with the prosaic name of “G protein–coupled receptor, family C, group 5, member D” or simply GPRC5D. The antigen is a so-called “orphan” receptor with an unidentified ligand. The receptor is expressed in malignant plasma cells, making it a particularly attractive target for the treatment of patients with multiple myeloma.
“It’s important to pick the right target for these [patients] and GPRC5D is a good candidate for that because it’s highly expressed on myeloma cells but spares normal tissues, in particular the hematopoietic stem cells for the precursors to their blood,” Dr. Chari said.
The new drug could be available next year. The manufacturer, Janssen, announced last week that it had submitted an approval application with the Food and Drug Administration for talquetamab use in the treatment of patients with relapsed or refractory multiple myeloma.
The clinical results so far “indicate the potential of this treatment for heavily pretreated patients who have exhausted currently approved therapies,” Dr. Chari said in a statement.
MonumenTAL study
Dr. Chari and colleagues recently reported results of the phase 1 MonumenTAL-1 study in The New England Journal of Medicine. At ASH 2022, they reported phase 2 results from the same study, including some patients carried over from phase 1, but also a subgroup of patients with prior exposure to either chimeric antigen receptor T-cell (CAR-T) therapy or other bispecific T cell-engaging antibodies.
In the phase 1 dose-escalation study published in NEJM, the response rates among patients who had a median of six prior lines of therapy ranged from 64% to 70%. The drug was delivered in this phase at a variety of dose levels and schedules, and both intravenously and subcutaneously.
Three cohorts, two doses
The phase 2 study enrolled patients who had a minimum of three prior lines of therapy including a proteasome inhibitor, immunomodulating agent, and anti-CD38 antibody, and who had good-to-fair performance status.
There were three cohorts. The first cohort comprised 21 patients from phase 1 and 122 from phase 2 who received talquetamab at a dose of 0.4 mg/kg subcutaneously once weekly. These patients were allowed to have received prior therapy with an antibody-drug conjugate (ADC) targeted against B-cell maturation antigen (BCMA), but could not have received a prior T-cell redirection therapy.
The second cohort comprised 36 patients in phase 1 and 109 in phase 2 who were treated with 0.8 mg/kg subcutaneously every 2 weeks. These patients had the same prior therapy allowances and restrictions as the first cohort.
The third cohort comprised 17 patients in phase 1 plus 34 patients in phase 2 who had received either CAR T-cell receptor therapy or a different bispecific T-cell engager. These patients received either 0.4 mg/kg weekly subcutaneous talquetamab, or 0.8 mg/kg every 2 weeks.
Phase 2 results
The overall response rate (ORR) among patients treated at 0.4 mg/kg weekly was 74.1%, including 23.8% stringent complete responses (sCR), 9.8% complete response (CR), 25.9% very good partial responses (VGPR) and 14.7% partial responses (PR).
The ORR among patients treated at the 0.8 mg/kg every 2 week dose was 73.1%, consisting of 20% sCR, 12.4% CR, 24,8% VGPR, and 15.9% PR.
The response rates were consistent across subgroups, including baseline International Staging System (ISS) stage III disease, baseline cytogenetic risk, number of prior therapies, degree of refractoriness to prior therapy, and prior exposure to the anti-BCMA antibody belantamab (except patients with baseline plasmacytomas).
The median durations of responses were 9.3 months and 13 months in the 0.4 and 0.8 mg/kg doses, respectively. The median duration of response was not reached among patients who had achieved a CR or better in either dosing group.
Safety profile
Most adverse events of grade 3 or 4 were cytopenias, including anemia, neutropenia, lymphopenia, and thrombocytopenia. These adverse events were generally limited to the first three cycles, and less than a third of all cytopenias were grade 3 or greater.
Infection occurred in 57.3% of patients treated at 0.4 mg/kg weekly and 50.3% treated at 0.8 mg/kg every 2 weeks. Of these infections, 16.8% and 11.7%, respectively, were grade 3 or 4.
Opportunistic infections were seen in 3.5% of patients treated at 0.4 mg/kg and 2.8% of those treated at 0.8 mg/kg.
Taste alterations (dysgeusia) occurred in nearly half of patients in each dosing group. Dysgeusia was managed with supportive care, including hydration, and in some cases with dose reductions.
Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 10% to 11% of patients, but most of these events were grade 1 or 2.
What’s next?
At the briefing, this news organization asked Dr. Chari whether, given the evident efficacy and relative safety of this agent, it could be moved up higher in the therapeutic lines and combined with other agents such as proteasome inhibitors (bortezomib et al.), immunomodulators (lenalidomide and others) and CD38-directed antibodies (daratumumab, etc.)
Dr. Chari replied that several studies combining talquetamab with agents in all of these classes and with other bispecific T-cell engagers are currently underway.
Dr. Chari disclosed consulting fees from Janssen, which supported the study. Dr. Lee has received clinical trial research funding from Amgen, AstraZeneca, Incyte, Kadmon, Novartis, Pfizer, Syndax, and Takeda and has served as a consultant to Incyte.
A version of this article first appeared on Medscape.com.
AT ASH 2022
Pricey gene therapy looks cost-effective for SCD
NEW ORLEANS –
Another gene therapy, a treatment for sickle cell anemia now in late clinical development, is expected to come on the market soon. It, too, is expected to bear an exorbitant price tag.
Such potentially curative therapies put financial pressure on publicly and privately funded health insurance.
However, investigators said that the new treatment for patients with sickle cell disease (SCD) in the United States has the potential to be cost-effective. Those who analyzed the costs used a novel method that takes historical health inequities into account.
“When faced with costs of innovative, one-time-administered therapies, budgetary constraints, as we all know too well, can and have driven therapy availability or lack thereof for patients,” said George Goshua, MD, from the Yale University, New Haven, Conn., speaking here at the annual meeting of the American Society of Hematology.
“We believe that quantitative consideration of health inequities, in addition to the important quality considerations, may be an additional helpful metric in this decision-making context,” he said.
He noted that SCD predominantly affects Black Americans, “who have historically been a very marginalized population when it comes to health care.
“Our study shows that, when we compare the costs of gene therapy and existing standard-of-care treatment for SCD using a technique that accounts for historical health disparities, gene therapy could be an equitable therapeutic strategy for all patients with SCD, whether their disease is mild, moderate, or severe,” he said.
Commenting on the study for this news organization, Bosula Oluwole, MD, from the University of Washington, Seattle, who studies sickle cell disease but was not involved in this study, said the cost-analysis approach taken by Dr. Goshua and colleagues is interesting, but she added: “I think we still have a way to go in trying to fully understand the issue.
“When you look over time at the cost for a patient to get gene therapy vs. the standard of care, it might actually be beneficial to have the gene therapy,” Dr. Oluwole said.
She noted, however, that some patients start gene therapy for SCD at older ages and that it’s important to analyze whether the treatment can still be cost-effective or the best therapeutic option for such patients.
Adding a D to CEA
Dr. Goshua and colleagues at Yale University and the Harvard T.H. Chan School of Public Health in Boston conducted what they believe is the first study in hematology to use distributional cost-effectiveness analysis (DCEA), developed at the University of York, England.
A University of York website explains that DCEA “is a general umbrella term for economic evaluation studies that provide information about equity in the distribution of costs and effects as well as efficiency in terms of aggregate costs and effects. DCEA can provide distributional breakdowns of who gains most and who bears the largest burdens (opportunity costs) by equity-relevant social variables (e.g., socioeconomic status, ethnicity, location) and disease categories (e.g., severity of illness, rarity, disability).”
The technique can also employ equity weight to evaluate trade-offs between equity and efficiency, the website says.
As Dr. Goshua put it, equity weighting is “a way of quantifying how much we prioritize health care equity.”
QALYs considered
Dr. Goshua and colleagues included equity weight in an analysis of 10 years of data on annual health care costs for patients with SCD who were covered by private insurance and were treated with medications (for example, hydroxyurea), antibiotics, blood transfusion, and hematopoietic stem cell transplants. Sex and the frequency of hospitalizations for acute pain crises were factors in the Markov model they created.
The model assumes that a single course of gene therapy for SCD would cost $2.1 million. The estimate was based on the cost of U.S. Food and Drug Administration–approved gene therapies, and it was assumed that the therapy would result in permanent disease remission for all patients.
In addition, the model assumed that all eligible patients in the United States with SCD who are aged 12 years and older would be offered the gene therapy.
In their base-case analysis, gene therapy starting at age 12 would yield 25.5 discounted lifetime quality-adjusted life-years (QALYs) at a cost of $2.4 million, compared with 16.0 discounted lifetime QALYs at a cost of $1.1 million for standard care.
Under traditional cost-effectiveness calculations, the upper limit of the incremental cost-effectiveness ratio (ICER) is estimated to be $100,000 per QALY. Under this scenario, the ICER of gene therapy for SCD at $144,000 per QALY would be considered by health economists or insurers to be too steep a price to pay.
However, applying equity weighting to the formula would bring the price of gene therapy into the $1.4 million to $3 million range.
Dr. Goshua acknowledged that the study is limited by the assumption that gene therapy would be a one-time cost and that patients would not need to undergo repeat therapy or treatment for relapses.
Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Center in Seattle, and a former ASH president, who moderated a briefing the day before Dr. Goshua presented his data, recommended that he and his colleagues use their technique to explore other health inequities, such as in the care of patients with multiple myeloma.
“There’s some evidence that Black patients are not using even the agents we have as [are] some of the other groups, so there may be some distributional inequities there as well,” she said.
The study was funded by ASH and the Yale School of Medicine. Dr. Goshua, Dr. Oluwole, and Dr. Lee have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
NEW ORLEANS –
Another gene therapy, a treatment for sickle cell anemia now in late clinical development, is expected to come on the market soon. It, too, is expected to bear an exorbitant price tag.
Such potentially curative therapies put financial pressure on publicly and privately funded health insurance.
However, investigators said that the new treatment for patients with sickle cell disease (SCD) in the United States has the potential to be cost-effective. Those who analyzed the costs used a novel method that takes historical health inequities into account.
“When faced with costs of innovative, one-time-administered therapies, budgetary constraints, as we all know too well, can and have driven therapy availability or lack thereof for patients,” said George Goshua, MD, from the Yale University, New Haven, Conn., speaking here at the annual meeting of the American Society of Hematology.
“We believe that quantitative consideration of health inequities, in addition to the important quality considerations, may be an additional helpful metric in this decision-making context,” he said.
He noted that SCD predominantly affects Black Americans, “who have historically been a very marginalized population when it comes to health care.
“Our study shows that, when we compare the costs of gene therapy and existing standard-of-care treatment for SCD using a technique that accounts for historical health disparities, gene therapy could be an equitable therapeutic strategy for all patients with SCD, whether their disease is mild, moderate, or severe,” he said.
Commenting on the study for this news organization, Bosula Oluwole, MD, from the University of Washington, Seattle, who studies sickle cell disease but was not involved in this study, said the cost-analysis approach taken by Dr. Goshua and colleagues is interesting, but she added: “I think we still have a way to go in trying to fully understand the issue.
“When you look over time at the cost for a patient to get gene therapy vs. the standard of care, it might actually be beneficial to have the gene therapy,” Dr. Oluwole said.
She noted, however, that some patients start gene therapy for SCD at older ages and that it’s important to analyze whether the treatment can still be cost-effective or the best therapeutic option for such patients.
Adding a D to CEA
Dr. Goshua and colleagues at Yale University and the Harvard T.H. Chan School of Public Health in Boston conducted what they believe is the first study in hematology to use distributional cost-effectiveness analysis (DCEA), developed at the University of York, England.
A University of York website explains that DCEA “is a general umbrella term for economic evaluation studies that provide information about equity in the distribution of costs and effects as well as efficiency in terms of aggregate costs and effects. DCEA can provide distributional breakdowns of who gains most and who bears the largest burdens (opportunity costs) by equity-relevant social variables (e.g., socioeconomic status, ethnicity, location) and disease categories (e.g., severity of illness, rarity, disability).”
The technique can also employ equity weight to evaluate trade-offs between equity and efficiency, the website says.
As Dr. Goshua put it, equity weighting is “a way of quantifying how much we prioritize health care equity.”
QALYs considered
Dr. Goshua and colleagues included equity weight in an analysis of 10 years of data on annual health care costs for patients with SCD who were covered by private insurance and were treated with medications (for example, hydroxyurea), antibiotics, blood transfusion, and hematopoietic stem cell transplants. Sex and the frequency of hospitalizations for acute pain crises were factors in the Markov model they created.
The model assumes that a single course of gene therapy for SCD would cost $2.1 million. The estimate was based on the cost of U.S. Food and Drug Administration–approved gene therapies, and it was assumed that the therapy would result in permanent disease remission for all patients.
In addition, the model assumed that all eligible patients in the United States with SCD who are aged 12 years and older would be offered the gene therapy.
In their base-case analysis, gene therapy starting at age 12 would yield 25.5 discounted lifetime quality-adjusted life-years (QALYs) at a cost of $2.4 million, compared with 16.0 discounted lifetime QALYs at a cost of $1.1 million for standard care.
Under traditional cost-effectiveness calculations, the upper limit of the incremental cost-effectiveness ratio (ICER) is estimated to be $100,000 per QALY. Under this scenario, the ICER of gene therapy for SCD at $144,000 per QALY would be considered by health economists or insurers to be too steep a price to pay.
However, applying equity weighting to the formula would bring the price of gene therapy into the $1.4 million to $3 million range.
Dr. Goshua acknowledged that the study is limited by the assumption that gene therapy would be a one-time cost and that patients would not need to undergo repeat therapy or treatment for relapses.
Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Center in Seattle, and a former ASH president, who moderated a briefing the day before Dr. Goshua presented his data, recommended that he and his colleagues use their technique to explore other health inequities, such as in the care of patients with multiple myeloma.
“There’s some evidence that Black patients are not using even the agents we have as [are] some of the other groups, so there may be some distributional inequities there as well,” she said.
The study was funded by ASH and the Yale School of Medicine. Dr. Goshua, Dr. Oluwole, and Dr. Lee have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
NEW ORLEANS –
Another gene therapy, a treatment for sickle cell anemia now in late clinical development, is expected to come on the market soon. It, too, is expected to bear an exorbitant price tag.
Such potentially curative therapies put financial pressure on publicly and privately funded health insurance.
However, investigators said that the new treatment for patients with sickle cell disease (SCD) in the United States has the potential to be cost-effective. Those who analyzed the costs used a novel method that takes historical health inequities into account.
“When faced with costs of innovative, one-time-administered therapies, budgetary constraints, as we all know too well, can and have driven therapy availability or lack thereof for patients,” said George Goshua, MD, from the Yale University, New Haven, Conn., speaking here at the annual meeting of the American Society of Hematology.
“We believe that quantitative consideration of health inequities, in addition to the important quality considerations, may be an additional helpful metric in this decision-making context,” he said.
He noted that SCD predominantly affects Black Americans, “who have historically been a very marginalized population when it comes to health care.
“Our study shows that, when we compare the costs of gene therapy and existing standard-of-care treatment for SCD using a technique that accounts for historical health disparities, gene therapy could be an equitable therapeutic strategy for all patients with SCD, whether their disease is mild, moderate, or severe,” he said.
Commenting on the study for this news organization, Bosula Oluwole, MD, from the University of Washington, Seattle, who studies sickle cell disease but was not involved in this study, said the cost-analysis approach taken by Dr. Goshua and colleagues is interesting, but she added: “I think we still have a way to go in trying to fully understand the issue.
“When you look over time at the cost for a patient to get gene therapy vs. the standard of care, it might actually be beneficial to have the gene therapy,” Dr. Oluwole said.
She noted, however, that some patients start gene therapy for SCD at older ages and that it’s important to analyze whether the treatment can still be cost-effective or the best therapeutic option for such patients.
Adding a D to CEA
Dr. Goshua and colleagues at Yale University and the Harvard T.H. Chan School of Public Health in Boston conducted what they believe is the first study in hematology to use distributional cost-effectiveness analysis (DCEA), developed at the University of York, England.
A University of York website explains that DCEA “is a general umbrella term for economic evaluation studies that provide information about equity in the distribution of costs and effects as well as efficiency in terms of aggregate costs and effects. DCEA can provide distributional breakdowns of who gains most and who bears the largest burdens (opportunity costs) by equity-relevant social variables (e.g., socioeconomic status, ethnicity, location) and disease categories (e.g., severity of illness, rarity, disability).”
The technique can also employ equity weight to evaluate trade-offs between equity and efficiency, the website says.
As Dr. Goshua put it, equity weighting is “a way of quantifying how much we prioritize health care equity.”
QALYs considered
Dr. Goshua and colleagues included equity weight in an analysis of 10 years of data on annual health care costs for patients with SCD who were covered by private insurance and were treated with medications (for example, hydroxyurea), antibiotics, blood transfusion, and hematopoietic stem cell transplants. Sex and the frequency of hospitalizations for acute pain crises were factors in the Markov model they created.
The model assumes that a single course of gene therapy for SCD would cost $2.1 million. The estimate was based on the cost of U.S. Food and Drug Administration–approved gene therapies, and it was assumed that the therapy would result in permanent disease remission for all patients.
In addition, the model assumed that all eligible patients in the United States with SCD who are aged 12 years and older would be offered the gene therapy.
In their base-case analysis, gene therapy starting at age 12 would yield 25.5 discounted lifetime quality-adjusted life-years (QALYs) at a cost of $2.4 million, compared with 16.0 discounted lifetime QALYs at a cost of $1.1 million for standard care.
Under traditional cost-effectiveness calculations, the upper limit of the incremental cost-effectiveness ratio (ICER) is estimated to be $100,000 per QALY. Under this scenario, the ICER of gene therapy for SCD at $144,000 per QALY would be considered by health economists or insurers to be too steep a price to pay.
However, applying equity weighting to the formula would bring the price of gene therapy into the $1.4 million to $3 million range.
Dr. Goshua acknowledged that the study is limited by the assumption that gene therapy would be a one-time cost and that patients would not need to undergo repeat therapy or treatment for relapses.
Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Center in Seattle, and a former ASH president, who moderated a briefing the day before Dr. Goshua presented his data, recommended that he and his colleagues use their technique to explore other health inequities, such as in the care of patients with multiple myeloma.
“There’s some evidence that Black patients are not using even the agents we have as [are] some of the other groups, so there may be some distributional inequities there as well,” she said.
The study was funded by ASH and the Yale School of Medicine. Dr. Goshua, Dr. Oluwole, and Dr. Lee have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ASH 2022