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Ixazomib targets treatment failure in chronic GVHD
HOUSTON –
Patients who received ixazomib in this trial had a lower rate of treatment failure – a composite endpoint of death, relapse, and need for additional systemic immunosuppressive therapy – than that of historical controls.
Joseph Pidala, MD, PhD, of Moffitt Cancer Center in Tampa, Fla., presented this finding at the Transplantation & Cellular Therapy Meetings.
The trial (NCT02513498) included 50 patients with a median age of 58 years (range, 44-65). Patients had acute leukemia (52%), lymphoma (18%), chronic leukemia (12%), myelodysplastic syndromes/myeloproliferative neoplasms (8%), and myeloma (4%).
Most patients (90%) received peripheral blood transplants, but 10% received bone marrow. Patients had matched unrelated donors (48%), matched related donors (44%), mismatched unrelated donors (6%), and mismatched related donors (2%).
Most patients (84%) had severe cGVHD, but 16% had moderate cGVHD. About half of patients (52%) had four or more organs involved, and 78% received three or more prior lines of systemic therapy for cGVHD. The median time from cGVHD onset to trial enrollment was 33.5 months.
“[I]t was an advanced population that was highly treatment experienced,” Dr. Pidala said.
Initially, patients received ixazomib at 4 mg on days 1, 8, and 15 of a 28-day cycle for up to six cycles. However, the protocol was amended to allow additional cycles for responders.
Fifty-two percent of patients (n = 26) completed at least six cycles of therapy. The remaining patients stopped treatment because of unresolved toxicity, treatment failure, withdrawal, noncompliance, and death.
“Seven patients, in total, did continue therapy beyond six cycles,” Dr. Pidala said. “Six of these had partial response at 6 months, and one had stable disease.”
The overall response rate at 6 months was 40%. All 20 responders had partial responses.
The 6-month treatment failure rate was significantly lower in this trial than in historical controls (Blood 2013 121:2340-6). The rates of treatment failure were 28% and 44%, respectively (P = .01).
Treatment failure was largely due to the need for additional treatment, Dr. Pidala noted. Relapse and nonrelapse mortality were “uncommon” in this trial.
The investigators did not find any patient, transplant, or cGVHD-related factors significantly associated with 6-month treatment failure.
The failure-free survival rate at 6 months was 72% in this trial and 56% in historical controls. The failure-free survival rate at 12 months was 57% and 45%, respectively.
Serious adverse events occurred in 38% of patients on this trial. Patients required ixazomib dose reductions due to thrombocytopenia, fatigue, diarrhea, and infection.
There were five deaths, and two of them were considered possibly related to ixazomib.
“This was driven by the proximity of the death events to the last dose of ixazomib, specifically, within 1 month,” Dr. Pidala said. “One of these death events was a case of respiratory failure. The other was a case of sudden, unexplained death.”
The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At the meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
Dr. Pidala reported having nothing to disclose. Other investigators reported relationships with Pfizer, CSL Behring, Agios, Incyte, Genentech, and Takeda. The trial was sponsored by the Fred Hutchinson Cancer Research Center in collaboration with the National Cancer Institute.
SOURCE: Pidala J et al. TCT 2019, Abstract 35.
HOUSTON –
Patients who received ixazomib in this trial had a lower rate of treatment failure – a composite endpoint of death, relapse, and need for additional systemic immunosuppressive therapy – than that of historical controls.
Joseph Pidala, MD, PhD, of Moffitt Cancer Center in Tampa, Fla., presented this finding at the Transplantation & Cellular Therapy Meetings.
The trial (NCT02513498) included 50 patients with a median age of 58 years (range, 44-65). Patients had acute leukemia (52%), lymphoma (18%), chronic leukemia (12%), myelodysplastic syndromes/myeloproliferative neoplasms (8%), and myeloma (4%).
Most patients (90%) received peripheral blood transplants, but 10% received bone marrow. Patients had matched unrelated donors (48%), matched related donors (44%), mismatched unrelated donors (6%), and mismatched related donors (2%).
Most patients (84%) had severe cGVHD, but 16% had moderate cGVHD. About half of patients (52%) had four or more organs involved, and 78% received three or more prior lines of systemic therapy for cGVHD. The median time from cGVHD onset to trial enrollment was 33.5 months.
“[I]t was an advanced population that was highly treatment experienced,” Dr. Pidala said.
Initially, patients received ixazomib at 4 mg on days 1, 8, and 15 of a 28-day cycle for up to six cycles. However, the protocol was amended to allow additional cycles for responders.
Fifty-two percent of patients (n = 26) completed at least six cycles of therapy. The remaining patients stopped treatment because of unresolved toxicity, treatment failure, withdrawal, noncompliance, and death.
“Seven patients, in total, did continue therapy beyond six cycles,” Dr. Pidala said. “Six of these had partial response at 6 months, and one had stable disease.”
The overall response rate at 6 months was 40%. All 20 responders had partial responses.
The 6-month treatment failure rate was significantly lower in this trial than in historical controls (Blood 2013 121:2340-6). The rates of treatment failure were 28% and 44%, respectively (P = .01).
Treatment failure was largely due to the need for additional treatment, Dr. Pidala noted. Relapse and nonrelapse mortality were “uncommon” in this trial.
The investigators did not find any patient, transplant, or cGVHD-related factors significantly associated with 6-month treatment failure.
The failure-free survival rate at 6 months was 72% in this trial and 56% in historical controls. The failure-free survival rate at 12 months was 57% and 45%, respectively.
Serious adverse events occurred in 38% of patients on this trial. Patients required ixazomib dose reductions due to thrombocytopenia, fatigue, diarrhea, and infection.
There were five deaths, and two of them were considered possibly related to ixazomib.
“This was driven by the proximity of the death events to the last dose of ixazomib, specifically, within 1 month,” Dr. Pidala said. “One of these death events was a case of respiratory failure. The other was a case of sudden, unexplained death.”
The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At the meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
Dr. Pidala reported having nothing to disclose. Other investigators reported relationships with Pfizer, CSL Behring, Agios, Incyte, Genentech, and Takeda. The trial was sponsored by the Fred Hutchinson Cancer Research Center in collaboration with the National Cancer Institute.
SOURCE: Pidala J et al. TCT 2019, Abstract 35.
HOUSTON –
Patients who received ixazomib in this trial had a lower rate of treatment failure – a composite endpoint of death, relapse, and need for additional systemic immunosuppressive therapy – than that of historical controls.
Joseph Pidala, MD, PhD, of Moffitt Cancer Center in Tampa, Fla., presented this finding at the Transplantation & Cellular Therapy Meetings.
The trial (NCT02513498) included 50 patients with a median age of 58 years (range, 44-65). Patients had acute leukemia (52%), lymphoma (18%), chronic leukemia (12%), myelodysplastic syndromes/myeloproliferative neoplasms (8%), and myeloma (4%).
Most patients (90%) received peripheral blood transplants, but 10% received bone marrow. Patients had matched unrelated donors (48%), matched related donors (44%), mismatched unrelated donors (6%), and mismatched related donors (2%).
Most patients (84%) had severe cGVHD, but 16% had moderate cGVHD. About half of patients (52%) had four or more organs involved, and 78% received three or more prior lines of systemic therapy for cGVHD. The median time from cGVHD onset to trial enrollment was 33.5 months.
“[I]t was an advanced population that was highly treatment experienced,” Dr. Pidala said.
Initially, patients received ixazomib at 4 mg on days 1, 8, and 15 of a 28-day cycle for up to six cycles. However, the protocol was amended to allow additional cycles for responders.
Fifty-two percent of patients (n = 26) completed at least six cycles of therapy. The remaining patients stopped treatment because of unresolved toxicity, treatment failure, withdrawal, noncompliance, and death.
“Seven patients, in total, did continue therapy beyond six cycles,” Dr. Pidala said. “Six of these had partial response at 6 months, and one had stable disease.”
The overall response rate at 6 months was 40%. All 20 responders had partial responses.
The 6-month treatment failure rate was significantly lower in this trial than in historical controls (Blood 2013 121:2340-6). The rates of treatment failure were 28% and 44%, respectively (P = .01).
Treatment failure was largely due to the need for additional treatment, Dr. Pidala noted. Relapse and nonrelapse mortality were “uncommon” in this trial.
The investigators did not find any patient, transplant, or cGVHD-related factors significantly associated with 6-month treatment failure.
The failure-free survival rate at 6 months was 72% in this trial and 56% in historical controls. The failure-free survival rate at 12 months was 57% and 45%, respectively.
Serious adverse events occurred in 38% of patients on this trial. Patients required ixazomib dose reductions due to thrombocytopenia, fatigue, diarrhea, and infection.
There were five deaths, and two of them were considered possibly related to ixazomib.
“This was driven by the proximity of the death events to the last dose of ixazomib, specifically, within 1 month,” Dr. Pidala said. “One of these death events was a case of respiratory failure. The other was a case of sudden, unexplained death.”
The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At the meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
Dr. Pidala reported having nothing to disclose. Other investigators reported relationships with Pfizer, CSL Behring, Agios, Incyte, Genentech, and Takeda. The trial was sponsored by the Fred Hutchinson Cancer Research Center in collaboration with the National Cancer Institute.
SOURCE: Pidala J et al. TCT 2019, Abstract 35.
REPORTING FROM TCT 2019
Key clinical point: Ixazomib may reduce treatment failure in patients with advanced chronic graft-versus-host disease.
Major finding: The 6-month treatment failure rate was significantly lower in this trial than in historical controls – 28% and 44%, respectively (P = .01).
Study details: A phase 2 trial of 50 patients with hematologic malignancies.
Disclosures: The trial was sponsored by the Fred Hutchinson Cancer Research Center in collaboration with the National Cancer Institute. The investigators reported relationships with Pfizer, CSL Behring, Agios, Incyte, Genentech, and Takeda.
Source: Pidala J et al. TCT 2019, Abstract 35.
Post-HCT azithromycin doesn’t increase relapse risk, study suggests
HOUSTON — When given after transplant, azithromycin does not increase the risk of relapse in patients with moderate to severe chronic graft-versus-host disease (cGVHD) and bronchiolitis obliterans syndrome (BOS), according to a retrospective study.
A prior study, ALLOZITHRO (JAMA. 2017 Aug 8;318[6]:557-66), showed an increased risk of relapse and death in patients who received azithromycin as BOS prophylaxis prior to hematopoietic cell transplant (HCT).
That discovery prompted the Food and Drug Administration to release a safety communication warning prescribers about the risks associated with azithromycin as BOS prophylaxis. However, it wasn’t clear if the same risks exist when azithromycin is given for cGVHD management after HCT.
To gain some insight, Mark Shamoun, MD, of the University of Michigan, Ann Arbor, and his colleagues examined data on patients with moderate to severe cGVHD and BOS who received azithromycin after undergoing HCT to treat a hematologic malignancy.
Dr. Shamoun presented the group’s findings at the Transplantation & Cellular Therapy Meetings.
The researchers reviewed data on 239 patients enrolled in the University of Michigan’s HCT database from 2010 to 2017. The median age at baseline was 55 years (range, 4-72 years).
The patients received transplants to treat acute myeloid leukemia or myelodysplastic syndromes (n = 141), acute lymphoblastic leukemia (n = 40), lymphoma (n = 26), chronic leukemia (n = 24), multiple myeloma (n = 6), and myeloproliferative neoplasms (n = 2).
The patients had matched related donors (43%) or matched unrelated donors (57%). Most patients received peripheral blood transplants (84%), though some received bone marrow (14%) or cord blood (2%). All patients had moderate (38%) or severe (62%) cGVHD.
Patients were split into two cohorts. Patients in cohort A (n = 86) had BOS and received azithromycin for more than 14 days.
Patients in cohort B (n = 153) either did not receive azithromycin or received it for 14 days or less. Fewer than 5% of patients in cohort B had BOS.
Most other baseline characteristics were similar between the cohorts. However, severe cGVHD was more prevalent in cohort A than B — 78% and 51%, respectively.
In cohort A, the median time to the start of azithromycin was 15 months after HCT (range, 3-68 months). The median duration of azithromycin treatment was 26 months (range, 1-77 months).
Results
The 2-year relapse rate was significantly lower in patients who received azithromycin than in those who did not — 4% and 17%, respectively (P = .001).
There was a significant difference in relapse rate both from the time of HCT (P = .001) and from the start of azithromycin or cGVHD (P = .011).
There was no significant difference in overall survival between the cohorts, either from the time of HCT (P = .294) or from the start of azithromycin or cGVHD (P = .428).
Dr. Shamoun said these results suggest azithromycin does not increase the risk of relapse when it is used to manage cGVHD. However, this study is limited by its retrospective nature. In addition, most patients in cohort B did not have BOS, severe cGVHD was more common in cohort A, and the incidence of relapse was not calculated from the time of azithromycin initiation in both cohorts. Therefore, additional investigation is needed.
Dr. Shamoun presented these results at Transplantation & Cellular Therapy Meetings, which is held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At the meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society, the American Society for Transplantation and Cellular Therapy (ASTCT).
Dr. Shamoun reported no conflicts of interest.
SOURCE: Shamoun M et al. TCT 2019, Abstract 33.
HOUSTON — When given after transplant, azithromycin does not increase the risk of relapse in patients with moderate to severe chronic graft-versus-host disease (cGVHD) and bronchiolitis obliterans syndrome (BOS), according to a retrospective study.
A prior study, ALLOZITHRO (JAMA. 2017 Aug 8;318[6]:557-66), showed an increased risk of relapse and death in patients who received azithromycin as BOS prophylaxis prior to hematopoietic cell transplant (HCT).
That discovery prompted the Food and Drug Administration to release a safety communication warning prescribers about the risks associated with azithromycin as BOS prophylaxis. However, it wasn’t clear if the same risks exist when azithromycin is given for cGVHD management after HCT.
To gain some insight, Mark Shamoun, MD, of the University of Michigan, Ann Arbor, and his colleagues examined data on patients with moderate to severe cGVHD and BOS who received azithromycin after undergoing HCT to treat a hematologic malignancy.
Dr. Shamoun presented the group’s findings at the Transplantation & Cellular Therapy Meetings.
The researchers reviewed data on 239 patients enrolled in the University of Michigan’s HCT database from 2010 to 2017. The median age at baseline was 55 years (range, 4-72 years).
The patients received transplants to treat acute myeloid leukemia or myelodysplastic syndromes (n = 141), acute lymphoblastic leukemia (n = 40), lymphoma (n = 26), chronic leukemia (n = 24), multiple myeloma (n = 6), and myeloproliferative neoplasms (n = 2).
The patients had matched related donors (43%) or matched unrelated donors (57%). Most patients received peripheral blood transplants (84%), though some received bone marrow (14%) or cord blood (2%). All patients had moderate (38%) or severe (62%) cGVHD.
Patients were split into two cohorts. Patients in cohort A (n = 86) had BOS and received azithromycin for more than 14 days.
Patients in cohort B (n = 153) either did not receive azithromycin or received it for 14 days or less. Fewer than 5% of patients in cohort B had BOS.
Most other baseline characteristics were similar between the cohorts. However, severe cGVHD was more prevalent in cohort A than B — 78% and 51%, respectively.
In cohort A, the median time to the start of azithromycin was 15 months after HCT (range, 3-68 months). The median duration of azithromycin treatment was 26 months (range, 1-77 months).
Results
The 2-year relapse rate was significantly lower in patients who received azithromycin than in those who did not — 4% and 17%, respectively (P = .001).
There was a significant difference in relapse rate both from the time of HCT (P = .001) and from the start of azithromycin or cGVHD (P = .011).
There was no significant difference in overall survival between the cohorts, either from the time of HCT (P = .294) or from the start of azithromycin or cGVHD (P = .428).
Dr. Shamoun said these results suggest azithromycin does not increase the risk of relapse when it is used to manage cGVHD. However, this study is limited by its retrospective nature. In addition, most patients in cohort B did not have BOS, severe cGVHD was more common in cohort A, and the incidence of relapse was not calculated from the time of azithromycin initiation in both cohorts. Therefore, additional investigation is needed.
Dr. Shamoun presented these results at Transplantation & Cellular Therapy Meetings, which is held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At the meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society, the American Society for Transplantation and Cellular Therapy (ASTCT).
Dr. Shamoun reported no conflicts of interest.
SOURCE: Shamoun M et al. TCT 2019, Abstract 33.
HOUSTON — When given after transplant, azithromycin does not increase the risk of relapse in patients with moderate to severe chronic graft-versus-host disease (cGVHD) and bronchiolitis obliterans syndrome (BOS), according to a retrospective study.
A prior study, ALLOZITHRO (JAMA. 2017 Aug 8;318[6]:557-66), showed an increased risk of relapse and death in patients who received azithromycin as BOS prophylaxis prior to hematopoietic cell transplant (HCT).
That discovery prompted the Food and Drug Administration to release a safety communication warning prescribers about the risks associated with azithromycin as BOS prophylaxis. However, it wasn’t clear if the same risks exist when azithromycin is given for cGVHD management after HCT.
To gain some insight, Mark Shamoun, MD, of the University of Michigan, Ann Arbor, and his colleagues examined data on patients with moderate to severe cGVHD and BOS who received azithromycin after undergoing HCT to treat a hematologic malignancy.
Dr. Shamoun presented the group’s findings at the Transplantation & Cellular Therapy Meetings.
The researchers reviewed data on 239 patients enrolled in the University of Michigan’s HCT database from 2010 to 2017. The median age at baseline was 55 years (range, 4-72 years).
The patients received transplants to treat acute myeloid leukemia or myelodysplastic syndromes (n = 141), acute lymphoblastic leukemia (n = 40), lymphoma (n = 26), chronic leukemia (n = 24), multiple myeloma (n = 6), and myeloproliferative neoplasms (n = 2).
The patients had matched related donors (43%) or matched unrelated donors (57%). Most patients received peripheral blood transplants (84%), though some received bone marrow (14%) or cord blood (2%). All patients had moderate (38%) or severe (62%) cGVHD.
Patients were split into two cohorts. Patients in cohort A (n = 86) had BOS and received azithromycin for more than 14 days.
Patients in cohort B (n = 153) either did not receive azithromycin or received it for 14 days or less. Fewer than 5% of patients in cohort B had BOS.
Most other baseline characteristics were similar between the cohorts. However, severe cGVHD was more prevalent in cohort A than B — 78% and 51%, respectively.
In cohort A, the median time to the start of azithromycin was 15 months after HCT (range, 3-68 months). The median duration of azithromycin treatment was 26 months (range, 1-77 months).
Results
The 2-year relapse rate was significantly lower in patients who received azithromycin than in those who did not — 4% and 17%, respectively (P = .001).
There was a significant difference in relapse rate both from the time of HCT (P = .001) and from the start of azithromycin or cGVHD (P = .011).
There was no significant difference in overall survival between the cohorts, either from the time of HCT (P = .294) or from the start of azithromycin or cGVHD (P = .428).
Dr. Shamoun said these results suggest azithromycin does not increase the risk of relapse when it is used to manage cGVHD. However, this study is limited by its retrospective nature. In addition, most patients in cohort B did not have BOS, severe cGVHD was more common in cohort A, and the incidence of relapse was not calculated from the time of azithromycin initiation in both cohorts. Therefore, additional investigation is needed.
Dr. Shamoun presented these results at Transplantation & Cellular Therapy Meetings, which is held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At the meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society, the American Society for Transplantation and Cellular Therapy (ASTCT).
Dr. Shamoun reported no conflicts of interest.
SOURCE: Shamoun M et al. TCT 2019, Abstract 33.
REPORTING FROM TCT 2019
Midostaurin maintenance may reduce relapse risk in FLT3-ITD+ AML
HOUSTON – Midostaurin maintenance therapy along with standard-of-care treatment after allogeneic stem cell transplant (alloSCT) in patients with acute myeloid leukemia (AML) appears to reduce the risk of relapse, according to findings from the randomized, phase 2 RADIUS trial.
Notably, the effect of midostaurin in this open-label, exploratory trial was most pronounced in patients with high levels of phosphorylated FLT3 (pFLT3) inhibition as assessed by plasma inhibitor activity assay, Richard T. Maziarz, MD, reported at the Transplantation & Cellular Therapy Meetings.
“The median [pFLT3 reduction] was less than 70% ... those patients who had the deepest level inhibition maintained the highest likelihood of staying free of disease,” Dr. Maziarz, a professor of medicine at Oregon Health & Science University, Portland, said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
Midostaurin is a multitargeted tyrosine kinase inhibitor (TKI) that was shown in the pivotal RATIFY trial to significantly improve event-free and overall survival versus placebo when interspersed with induction and consolidation chemotherapy and also when used for maintenance in adults with newly diagnosed FLT3-mutated AML, Dr. Maziarz explained. He noted that patients in the RATIFY study who underwent alloSCT did not receive midostaurin maintenance (N Engl J Med. 2017; 377:454-64).
Although alloSCT provides the greatest likelihood of sustained remission in AML, relapse rates remain high at 30%-59%, he said, adding that, “in the setting of transplantation, FLT3 expression, or FLT3-ITD [internal tandem duplication] ... is a poor risk feature.”
Studies are increasingly suggesting that posttransplant maintenance therapy may improve this outcome. For example, the small, randomized, phase 2 SORMAIN study presented at the 2018 annual meeting of the American Society of Hematology showed a signal for benefit with posttransplant maintenance with the TKI sorafenib. Data regarding midostaurin in this setting are limited, Dr. Maziarz noted.
The RADIUS trial was a small study designed to look for a similar signal with midostaurin and thus was not adequately powered to detect a statistical difference between the arms, he explained.
RADIUS included 60 AML patients aged 18-70 years who underwent myeloablative alloSCT and were in their first complete remission. The primary endpoint was relapse-free survival (RFS) at 18 months after transplant. Results were presented at ASH 2018.
RFS was 89% in 16 of 30 patients who were randomized to receive 50 mg of midostaurin twice daily along with standard-of-care (SOC) treatment and completed 12 4-week cycles. This compared with an RFS rate of 76% in 14 of 30 patients who received SOC only and completed 12 cycles (hazard ratio, 0.46).
The predicted relative reduction in the risk of relapse with the addition of midostaurin was 54%, and at 24 months, both RFS and overall survival were 85% in the midostaurin group and 76% in the SOC-only group, Dr. Maziarz reported.
The median duration of exposure to midostaurin was 10.5 months and the median dose intensity was 93 mg/day, indicating that full-dose therapy was achievable in most patients who stayed on the study.
Treatment was generally well tolerated; there was a comparable number of early discontinuations in the midostaurin and SOC-only arms. The discontinuations were caused mainly by adverse events (typically gastrointestinal toxicities) in the midostaurin arm and by consent withdrawal in the SOC-only arm, he said, adding that there were no significant differences between the groups with respect to serious adverse events or acute or chronic graft-versus-host disease.
Following the presentation of the primary RADIUS results at ASH 2018, an exploratory analysis was conducted to assess midostaurin’s inhibitory effects on FLT3 in plasma.
FLT3 plasma inhibitor activity, assessed by coculturing plasma samples taken on the first day of the treatment cycles with the FLT3-positive AML to look for a reduction in pFLT3, was evaluable in 28 patients in each arm.
“What we see is when you start there are high levels of FLT3, but the pFLT3 drops significantly with exposure to the plasma,” he said, noting that the effect was most prominent during the first two cycles of therapy.
The patients with the highest levels of inhibition had the greatest likelihood of RFS, whereas RFS in those with suboptimal pFLT3 inhibition was similar to that seen in the SOC-only arm, Dr. Maziarz said. Two patients in the midostaurin group who relapsed did so after 12 months – when midostaurin had been discontinued, he noted.
“Our conclusion is that maintenance midostaurin may contribute to a reduction in relapse risk at 18 months post transplant ... and can be safely administered in the posttransplant setting,” Dr. Maziarz said. “pFLT3 inhibition to less than 70% of baseline, at least in this study, was associated with improved relapse-free survival and overall survival, and it was achieved in more than 50% of patients on the midostaurin.”
It is likely that a more definitive answer will be provided by the Blood and Marrow Transplant Clinical Trials Network Protocol 1506, a large, multinational, placebo-controlled trial now recruiting to look at this question of whether maintenance therapy in the posttransplant setting will improve outcomes.
However, it is important to note that no patient in the RADIUS trial received pretransplant midostaurin, as RADIUS was conducted at the same time as the RATIFY trial.
“Patients today who will go to transplant with FLT3-ITD, the vast majority will have been treated during induction ... and we may have a totally different biology going forward,” he said.
Dr. Maziarz reported financial relationships with Incyte, Novartis, Celgene/Juno, Kite/Gilead, Juno Therapeutics, Kite Therapeutics, and Athersys.
HOUSTON – Midostaurin maintenance therapy along with standard-of-care treatment after allogeneic stem cell transplant (alloSCT) in patients with acute myeloid leukemia (AML) appears to reduce the risk of relapse, according to findings from the randomized, phase 2 RADIUS trial.
Notably, the effect of midostaurin in this open-label, exploratory trial was most pronounced in patients with high levels of phosphorylated FLT3 (pFLT3) inhibition as assessed by plasma inhibitor activity assay, Richard T. Maziarz, MD, reported at the Transplantation & Cellular Therapy Meetings.
“The median [pFLT3 reduction] was less than 70% ... those patients who had the deepest level inhibition maintained the highest likelihood of staying free of disease,” Dr. Maziarz, a professor of medicine at Oregon Health & Science University, Portland, said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
Midostaurin is a multitargeted tyrosine kinase inhibitor (TKI) that was shown in the pivotal RATIFY trial to significantly improve event-free and overall survival versus placebo when interspersed with induction and consolidation chemotherapy and also when used for maintenance in adults with newly diagnosed FLT3-mutated AML, Dr. Maziarz explained. He noted that patients in the RATIFY study who underwent alloSCT did not receive midostaurin maintenance (N Engl J Med. 2017; 377:454-64).
Although alloSCT provides the greatest likelihood of sustained remission in AML, relapse rates remain high at 30%-59%, he said, adding that, “in the setting of transplantation, FLT3 expression, or FLT3-ITD [internal tandem duplication] ... is a poor risk feature.”
Studies are increasingly suggesting that posttransplant maintenance therapy may improve this outcome. For example, the small, randomized, phase 2 SORMAIN study presented at the 2018 annual meeting of the American Society of Hematology showed a signal for benefit with posttransplant maintenance with the TKI sorafenib. Data regarding midostaurin in this setting are limited, Dr. Maziarz noted.
The RADIUS trial was a small study designed to look for a similar signal with midostaurin and thus was not adequately powered to detect a statistical difference between the arms, he explained.
RADIUS included 60 AML patients aged 18-70 years who underwent myeloablative alloSCT and were in their first complete remission. The primary endpoint was relapse-free survival (RFS) at 18 months after transplant. Results were presented at ASH 2018.
RFS was 89% in 16 of 30 patients who were randomized to receive 50 mg of midostaurin twice daily along with standard-of-care (SOC) treatment and completed 12 4-week cycles. This compared with an RFS rate of 76% in 14 of 30 patients who received SOC only and completed 12 cycles (hazard ratio, 0.46).
The predicted relative reduction in the risk of relapse with the addition of midostaurin was 54%, and at 24 months, both RFS and overall survival were 85% in the midostaurin group and 76% in the SOC-only group, Dr. Maziarz reported.
The median duration of exposure to midostaurin was 10.5 months and the median dose intensity was 93 mg/day, indicating that full-dose therapy was achievable in most patients who stayed on the study.
Treatment was generally well tolerated; there was a comparable number of early discontinuations in the midostaurin and SOC-only arms. The discontinuations were caused mainly by adverse events (typically gastrointestinal toxicities) in the midostaurin arm and by consent withdrawal in the SOC-only arm, he said, adding that there were no significant differences between the groups with respect to serious adverse events or acute or chronic graft-versus-host disease.
Following the presentation of the primary RADIUS results at ASH 2018, an exploratory analysis was conducted to assess midostaurin’s inhibitory effects on FLT3 in plasma.
FLT3 plasma inhibitor activity, assessed by coculturing plasma samples taken on the first day of the treatment cycles with the FLT3-positive AML to look for a reduction in pFLT3, was evaluable in 28 patients in each arm.
“What we see is when you start there are high levels of FLT3, but the pFLT3 drops significantly with exposure to the plasma,” he said, noting that the effect was most prominent during the first two cycles of therapy.
The patients with the highest levels of inhibition had the greatest likelihood of RFS, whereas RFS in those with suboptimal pFLT3 inhibition was similar to that seen in the SOC-only arm, Dr. Maziarz said. Two patients in the midostaurin group who relapsed did so after 12 months – when midostaurin had been discontinued, he noted.
“Our conclusion is that maintenance midostaurin may contribute to a reduction in relapse risk at 18 months post transplant ... and can be safely administered in the posttransplant setting,” Dr. Maziarz said. “pFLT3 inhibition to less than 70% of baseline, at least in this study, was associated with improved relapse-free survival and overall survival, and it was achieved in more than 50% of patients on the midostaurin.”
It is likely that a more definitive answer will be provided by the Blood and Marrow Transplant Clinical Trials Network Protocol 1506, a large, multinational, placebo-controlled trial now recruiting to look at this question of whether maintenance therapy in the posttransplant setting will improve outcomes.
However, it is important to note that no patient in the RADIUS trial received pretransplant midostaurin, as RADIUS was conducted at the same time as the RATIFY trial.
“Patients today who will go to transplant with FLT3-ITD, the vast majority will have been treated during induction ... and we may have a totally different biology going forward,” he said.
Dr. Maziarz reported financial relationships with Incyte, Novartis, Celgene/Juno, Kite/Gilead, Juno Therapeutics, Kite Therapeutics, and Athersys.
HOUSTON – Midostaurin maintenance therapy along with standard-of-care treatment after allogeneic stem cell transplant (alloSCT) in patients with acute myeloid leukemia (AML) appears to reduce the risk of relapse, according to findings from the randomized, phase 2 RADIUS trial.
Notably, the effect of midostaurin in this open-label, exploratory trial was most pronounced in patients with high levels of phosphorylated FLT3 (pFLT3) inhibition as assessed by plasma inhibitor activity assay, Richard T. Maziarz, MD, reported at the Transplantation & Cellular Therapy Meetings.
“The median [pFLT3 reduction] was less than 70% ... those patients who had the deepest level inhibition maintained the highest likelihood of staying free of disease,” Dr. Maziarz, a professor of medicine at Oregon Health & Science University, Portland, said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
Midostaurin is a multitargeted tyrosine kinase inhibitor (TKI) that was shown in the pivotal RATIFY trial to significantly improve event-free and overall survival versus placebo when interspersed with induction and consolidation chemotherapy and also when used for maintenance in adults with newly diagnosed FLT3-mutated AML, Dr. Maziarz explained. He noted that patients in the RATIFY study who underwent alloSCT did not receive midostaurin maintenance (N Engl J Med. 2017; 377:454-64).
Although alloSCT provides the greatest likelihood of sustained remission in AML, relapse rates remain high at 30%-59%, he said, adding that, “in the setting of transplantation, FLT3 expression, or FLT3-ITD [internal tandem duplication] ... is a poor risk feature.”
Studies are increasingly suggesting that posttransplant maintenance therapy may improve this outcome. For example, the small, randomized, phase 2 SORMAIN study presented at the 2018 annual meeting of the American Society of Hematology showed a signal for benefit with posttransplant maintenance with the TKI sorafenib. Data regarding midostaurin in this setting are limited, Dr. Maziarz noted.
The RADIUS trial was a small study designed to look for a similar signal with midostaurin and thus was not adequately powered to detect a statistical difference between the arms, he explained.
RADIUS included 60 AML patients aged 18-70 years who underwent myeloablative alloSCT and were in their first complete remission. The primary endpoint was relapse-free survival (RFS) at 18 months after transplant. Results were presented at ASH 2018.
RFS was 89% in 16 of 30 patients who were randomized to receive 50 mg of midostaurin twice daily along with standard-of-care (SOC) treatment and completed 12 4-week cycles. This compared with an RFS rate of 76% in 14 of 30 patients who received SOC only and completed 12 cycles (hazard ratio, 0.46).
The predicted relative reduction in the risk of relapse with the addition of midostaurin was 54%, and at 24 months, both RFS and overall survival were 85% in the midostaurin group and 76% in the SOC-only group, Dr. Maziarz reported.
The median duration of exposure to midostaurin was 10.5 months and the median dose intensity was 93 mg/day, indicating that full-dose therapy was achievable in most patients who stayed on the study.
Treatment was generally well tolerated; there was a comparable number of early discontinuations in the midostaurin and SOC-only arms. The discontinuations were caused mainly by adverse events (typically gastrointestinal toxicities) in the midostaurin arm and by consent withdrawal in the SOC-only arm, he said, adding that there were no significant differences between the groups with respect to serious adverse events or acute or chronic graft-versus-host disease.
Following the presentation of the primary RADIUS results at ASH 2018, an exploratory analysis was conducted to assess midostaurin’s inhibitory effects on FLT3 in plasma.
FLT3 plasma inhibitor activity, assessed by coculturing plasma samples taken on the first day of the treatment cycles with the FLT3-positive AML to look for a reduction in pFLT3, was evaluable in 28 patients in each arm.
“What we see is when you start there are high levels of FLT3, but the pFLT3 drops significantly with exposure to the plasma,” he said, noting that the effect was most prominent during the first two cycles of therapy.
The patients with the highest levels of inhibition had the greatest likelihood of RFS, whereas RFS in those with suboptimal pFLT3 inhibition was similar to that seen in the SOC-only arm, Dr. Maziarz said. Two patients in the midostaurin group who relapsed did so after 12 months – when midostaurin had been discontinued, he noted.
“Our conclusion is that maintenance midostaurin may contribute to a reduction in relapse risk at 18 months post transplant ... and can be safely administered in the posttransplant setting,” Dr. Maziarz said. “pFLT3 inhibition to less than 70% of baseline, at least in this study, was associated with improved relapse-free survival and overall survival, and it was achieved in more than 50% of patients on the midostaurin.”
It is likely that a more definitive answer will be provided by the Blood and Marrow Transplant Clinical Trials Network Protocol 1506, a large, multinational, placebo-controlled trial now recruiting to look at this question of whether maintenance therapy in the posttransplant setting will improve outcomes.
However, it is important to note that no patient in the RADIUS trial received pretransplant midostaurin, as RADIUS was conducted at the same time as the RATIFY trial.
“Patients today who will go to transplant with FLT3-ITD, the vast majority will have been treated during induction ... and we may have a totally different biology going forward,” he said.
Dr. Maziarz reported financial relationships with Incyte, Novartis, Celgene/Juno, Kite/Gilead, Juno Therapeutics, Kite Therapeutics, and Athersys.
REPORTING FROM TCT 2019
ZUMA-1 update: Axi-cel responses persist at 2 years
HOUSTON – With a median follow-up now exceeding 2 years, 39% of refractory large B-cell lymphoma patients enrolled in the pivotal ZUMA-1 trial have maintained ongoing response to axicabtagene ciloleucel, according to an investigator involved in the study.
Median duration of response to axi-cel and median overall survival have not yet been reached, while a recent subset analysis showed that nearly half of patients with certain high-risk characteristics had a durable response, said investigator Sattva S. Neelapu, MD, of the University of Texas MD Anderson Cancer Center, Houston.
Evidence of B-cell recovery and a decrease in detectable, gene-marked CAR T cells have been noted in further follow-up, suggesting that functional CAR T-cell persistence may not be required for long-term remissions, Dr. Neelapu added.
“These data support [the conclusion] that axi-cel induces durable remissions in patients with large B-cell lymphoma who otherwise lack curative options,” Dr. Neelapu said at the Transplantation & Cellular Therapy Meetings.
The update on the phase 1/2 ZUMA-1 study included 108 patients with refractory large B-cell lymphoma who received axi-cel, the CD19-directed autologous chimeric antigen receptor (CAR) T-cell therapy.
In a previously reported 1-year update on the trial, 42% of patients had ongoing responses, Dr. Neelapu said. In the present update, with a median follow-up of 27.1 months, ongoing responses were seen in 39%, most of whom (37%) were in complete response, according to the data presented.
Thirty-three patients in the phase 2 portion of ZUMA-1 were known to have double-expressor or high-grade B-cell lymphoma, according to the investigator. In this high-risk subset, 48% were in ongoing complete response at the 2-year follow-up.
Progression-free survival in ZUMA-1 plateaued at the 6 month-follow-up, according to Dr. Neelapu, who said that plateau has been largely maintained, with just 10 patients progressing since then. Median progression-free survival is 5.9 months and median overall survival has not been reached, with a 24-month overall survival of 51%.
Late-onset serious adverse events mainly consisted of manageable infections, none of which were considered related to axi-cel treatment, according to Dr. Neelapu.
The proportion of ongoing responders with detectable CAR T-cells has decreased over time, from 95% at 3 months to 66% at 24 months, Dr. Neelapu reported. Meanwhile, the proportion of ongoing responders with detectable B cells after axi-cel treatment has gone from 17% to 75%.
More details on the 2-year follow-up data from ZUMA-1 were reported recently in the Lancet Oncology (2019 Jan;20[1]:31-42).
Funding for ZUMA-1 came from Kite and the Leukemia & Lymphoma Society. Dr. Neelapu reported disclosures related to Kite, Celgene, Cellectis, Merck, Poseida, Acerta, Karus, Bristol-Myers Squibb, Novartis, and Unum Therapeutics.
The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
SOURCE: Neelapu SS et al. TCT 2019, Abstract 82.
HOUSTON – With a median follow-up now exceeding 2 years, 39% of refractory large B-cell lymphoma patients enrolled in the pivotal ZUMA-1 trial have maintained ongoing response to axicabtagene ciloleucel, according to an investigator involved in the study.
Median duration of response to axi-cel and median overall survival have not yet been reached, while a recent subset analysis showed that nearly half of patients with certain high-risk characteristics had a durable response, said investigator Sattva S. Neelapu, MD, of the University of Texas MD Anderson Cancer Center, Houston.
Evidence of B-cell recovery and a decrease in detectable, gene-marked CAR T cells have been noted in further follow-up, suggesting that functional CAR T-cell persistence may not be required for long-term remissions, Dr. Neelapu added.
“These data support [the conclusion] that axi-cel induces durable remissions in patients with large B-cell lymphoma who otherwise lack curative options,” Dr. Neelapu said at the Transplantation & Cellular Therapy Meetings.
The update on the phase 1/2 ZUMA-1 study included 108 patients with refractory large B-cell lymphoma who received axi-cel, the CD19-directed autologous chimeric antigen receptor (CAR) T-cell therapy.
In a previously reported 1-year update on the trial, 42% of patients had ongoing responses, Dr. Neelapu said. In the present update, with a median follow-up of 27.1 months, ongoing responses were seen in 39%, most of whom (37%) were in complete response, according to the data presented.
Thirty-three patients in the phase 2 portion of ZUMA-1 were known to have double-expressor or high-grade B-cell lymphoma, according to the investigator. In this high-risk subset, 48% were in ongoing complete response at the 2-year follow-up.
Progression-free survival in ZUMA-1 plateaued at the 6 month-follow-up, according to Dr. Neelapu, who said that plateau has been largely maintained, with just 10 patients progressing since then. Median progression-free survival is 5.9 months and median overall survival has not been reached, with a 24-month overall survival of 51%.
Late-onset serious adverse events mainly consisted of manageable infections, none of which were considered related to axi-cel treatment, according to Dr. Neelapu.
The proportion of ongoing responders with detectable CAR T-cells has decreased over time, from 95% at 3 months to 66% at 24 months, Dr. Neelapu reported. Meanwhile, the proportion of ongoing responders with detectable B cells after axi-cel treatment has gone from 17% to 75%.
More details on the 2-year follow-up data from ZUMA-1 were reported recently in the Lancet Oncology (2019 Jan;20[1]:31-42).
Funding for ZUMA-1 came from Kite and the Leukemia & Lymphoma Society. Dr. Neelapu reported disclosures related to Kite, Celgene, Cellectis, Merck, Poseida, Acerta, Karus, Bristol-Myers Squibb, Novartis, and Unum Therapeutics.
The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
SOURCE: Neelapu SS et al. TCT 2019, Abstract 82.
HOUSTON – With a median follow-up now exceeding 2 years, 39% of refractory large B-cell lymphoma patients enrolled in the pivotal ZUMA-1 trial have maintained ongoing response to axicabtagene ciloleucel, according to an investigator involved in the study.
Median duration of response to axi-cel and median overall survival have not yet been reached, while a recent subset analysis showed that nearly half of patients with certain high-risk characteristics had a durable response, said investigator Sattva S. Neelapu, MD, of the University of Texas MD Anderson Cancer Center, Houston.
Evidence of B-cell recovery and a decrease in detectable, gene-marked CAR T cells have been noted in further follow-up, suggesting that functional CAR T-cell persistence may not be required for long-term remissions, Dr. Neelapu added.
“These data support [the conclusion] that axi-cel induces durable remissions in patients with large B-cell lymphoma who otherwise lack curative options,” Dr. Neelapu said at the Transplantation & Cellular Therapy Meetings.
The update on the phase 1/2 ZUMA-1 study included 108 patients with refractory large B-cell lymphoma who received axi-cel, the CD19-directed autologous chimeric antigen receptor (CAR) T-cell therapy.
In a previously reported 1-year update on the trial, 42% of patients had ongoing responses, Dr. Neelapu said. In the present update, with a median follow-up of 27.1 months, ongoing responses were seen in 39%, most of whom (37%) were in complete response, according to the data presented.
Thirty-three patients in the phase 2 portion of ZUMA-1 were known to have double-expressor or high-grade B-cell lymphoma, according to the investigator. In this high-risk subset, 48% were in ongoing complete response at the 2-year follow-up.
Progression-free survival in ZUMA-1 plateaued at the 6 month-follow-up, according to Dr. Neelapu, who said that plateau has been largely maintained, with just 10 patients progressing since then. Median progression-free survival is 5.9 months and median overall survival has not been reached, with a 24-month overall survival of 51%.
Late-onset serious adverse events mainly consisted of manageable infections, none of which were considered related to axi-cel treatment, according to Dr. Neelapu.
The proportion of ongoing responders with detectable CAR T-cells has decreased over time, from 95% at 3 months to 66% at 24 months, Dr. Neelapu reported. Meanwhile, the proportion of ongoing responders with detectable B cells after axi-cel treatment has gone from 17% to 75%.
More details on the 2-year follow-up data from ZUMA-1 were reported recently in the Lancet Oncology (2019 Jan;20[1]:31-42).
Funding for ZUMA-1 came from Kite and the Leukemia & Lymphoma Society. Dr. Neelapu reported disclosures related to Kite, Celgene, Cellectis, Merck, Poseida, Acerta, Karus, Bristol-Myers Squibb, Novartis, and Unum Therapeutics.
The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
SOURCE: Neelapu SS et al. TCT 2019, Abstract 82.
REPORTING FROM TCT 2019
Dual-targeted CAR T shows ‘clinical signal’ in NHL
HOUSTON – A dual-targeted, locally manufactured, anti-CD19/CD20 chimeric antigen receptor (CAR) T-cell therapy was safe and produced ongoing complete responses in a phase 1 study of heavily pretreated non-Hodgkin lymphoma patients, an investigator reported.
The bispecific CAR T-cell product, designed to limit relapses due to loss of target antigen, was produced at the point of care with a 100% success rate for these heavily pretreated patients, the first of whom has now maintained a complete response for 19 months, said Parameswaran Hari, MD, of the Medical College of Wisconsin, Milwaukee.
“So far, this trial has demonstrated safety for this bispecific vector and suggests a clinical signal, with 7 out of 12 patients with ongoing CR, and with minimal toxicity,” Dr. Hari said at the Transplantation & Cellular Therapy Meetings.
“Point of care delivery, we think, allowed patients to have fresh infusion of CAR T cells, with the avoidance of cryopreservation,” added Dr. Hari, who presented the results on behalf of coinvestigators at the Medical College of Wisconsin and Lentigen Technology.
There was no grade 3 or 4 neurotoxicity or cytokine release syndrome among the 12 patients reported to date in the phase 1, dose-escalation trial, and no patient required intensive care, according to Dr. Hari. Grade 1 and 2 neurotoxicity occurred in two and one patients, respectively, while grade 1 and 2 cytokine release syndrome was observed in three patients each.
Among the 12 patients treated to date, the overall response rate was 81% at day 28, Dr. Hari said, noting that of 6 patients treated at the goal dose of 2.5 x 106 cells/kg, 5 remain in ongoing complete remission.
The median age of patients enrolled in the study was 55 years. Six patients had diffuse large B-cell lymphoma, five had mantle cell lymphoma, and two had chronic lymphocytic leukemia. All but one patient underwent fludarabine/cyclophosphamide lymphodepletion prior to receiving the inpatient CAR T-cell infusions, given over the course of 2 days.
Dr. Hari specifically highlighted the mantle cell lymphoma patient subset, noting that four out of five patients were in complete remission at day 28, and remained in ongoing complete remission at times ranging from 1 to 16 months.
With a set manufacturing time of 14 days, production was successful in all 12 patients, and 10 were able to receive fresh product, while 3 received cryopreserved product due to illness-related delays and a holiday, according to the investigators.
“The time to actual delivery of CAR T cell in the patient is actually shortened dramatically,” Dr. Hari said. “We hope to get it down to day 10.”
Local manufacturing can also reduce some costs associated with CAR T-cell production, such as shipping and courier costs, he added.
Taken together, these findings suggest that locally manufactured anti-CD19/CD20 CAR T cells could improve clinical outcomes for patients with relapsed and refractory B-cell NHL, with efficiency through point-of-care delivery, Dr. Hari concluded.
Further studies are planned to evaluate the efficacy of the product and to investigate the mechanism of relapse or progression in patients who experience treatment failure, he said.
Dr. Hari reported disclosures related to Juno, Kite, Spectrum, Janssen, Takeda, Celgene, and BMS. Several study coauthors reported that they were employed by Lentigen Technology, a Miltenyi Biotec Company.
The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
SOURCE: Shah NN et al. TCT 2019, Abstract 80.
HOUSTON – A dual-targeted, locally manufactured, anti-CD19/CD20 chimeric antigen receptor (CAR) T-cell therapy was safe and produced ongoing complete responses in a phase 1 study of heavily pretreated non-Hodgkin lymphoma patients, an investigator reported.
The bispecific CAR T-cell product, designed to limit relapses due to loss of target antigen, was produced at the point of care with a 100% success rate for these heavily pretreated patients, the first of whom has now maintained a complete response for 19 months, said Parameswaran Hari, MD, of the Medical College of Wisconsin, Milwaukee.
“So far, this trial has demonstrated safety for this bispecific vector and suggests a clinical signal, with 7 out of 12 patients with ongoing CR, and with minimal toxicity,” Dr. Hari said at the Transplantation & Cellular Therapy Meetings.
“Point of care delivery, we think, allowed patients to have fresh infusion of CAR T cells, with the avoidance of cryopreservation,” added Dr. Hari, who presented the results on behalf of coinvestigators at the Medical College of Wisconsin and Lentigen Technology.
There was no grade 3 or 4 neurotoxicity or cytokine release syndrome among the 12 patients reported to date in the phase 1, dose-escalation trial, and no patient required intensive care, according to Dr. Hari. Grade 1 and 2 neurotoxicity occurred in two and one patients, respectively, while grade 1 and 2 cytokine release syndrome was observed in three patients each.
Among the 12 patients treated to date, the overall response rate was 81% at day 28, Dr. Hari said, noting that of 6 patients treated at the goal dose of 2.5 x 106 cells/kg, 5 remain in ongoing complete remission.
The median age of patients enrolled in the study was 55 years. Six patients had diffuse large B-cell lymphoma, five had mantle cell lymphoma, and two had chronic lymphocytic leukemia. All but one patient underwent fludarabine/cyclophosphamide lymphodepletion prior to receiving the inpatient CAR T-cell infusions, given over the course of 2 days.
Dr. Hari specifically highlighted the mantle cell lymphoma patient subset, noting that four out of five patients were in complete remission at day 28, and remained in ongoing complete remission at times ranging from 1 to 16 months.
With a set manufacturing time of 14 days, production was successful in all 12 patients, and 10 were able to receive fresh product, while 3 received cryopreserved product due to illness-related delays and a holiday, according to the investigators.
“The time to actual delivery of CAR T cell in the patient is actually shortened dramatically,” Dr. Hari said. “We hope to get it down to day 10.”
Local manufacturing can also reduce some costs associated with CAR T-cell production, such as shipping and courier costs, he added.
Taken together, these findings suggest that locally manufactured anti-CD19/CD20 CAR T cells could improve clinical outcomes for patients with relapsed and refractory B-cell NHL, with efficiency through point-of-care delivery, Dr. Hari concluded.
Further studies are planned to evaluate the efficacy of the product and to investigate the mechanism of relapse or progression in patients who experience treatment failure, he said.
Dr. Hari reported disclosures related to Juno, Kite, Spectrum, Janssen, Takeda, Celgene, and BMS. Several study coauthors reported that they were employed by Lentigen Technology, a Miltenyi Biotec Company.
The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
SOURCE: Shah NN et al. TCT 2019, Abstract 80.
HOUSTON – A dual-targeted, locally manufactured, anti-CD19/CD20 chimeric antigen receptor (CAR) T-cell therapy was safe and produced ongoing complete responses in a phase 1 study of heavily pretreated non-Hodgkin lymphoma patients, an investigator reported.
The bispecific CAR T-cell product, designed to limit relapses due to loss of target antigen, was produced at the point of care with a 100% success rate for these heavily pretreated patients, the first of whom has now maintained a complete response for 19 months, said Parameswaran Hari, MD, of the Medical College of Wisconsin, Milwaukee.
“So far, this trial has demonstrated safety for this bispecific vector and suggests a clinical signal, with 7 out of 12 patients with ongoing CR, and with minimal toxicity,” Dr. Hari said at the Transplantation & Cellular Therapy Meetings.
“Point of care delivery, we think, allowed patients to have fresh infusion of CAR T cells, with the avoidance of cryopreservation,” added Dr. Hari, who presented the results on behalf of coinvestigators at the Medical College of Wisconsin and Lentigen Technology.
There was no grade 3 or 4 neurotoxicity or cytokine release syndrome among the 12 patients reported to date in the phase 1, dose-escalation trial, and no patient required intensive care, according to Dr. Hari. Grade 1 and 2 neurotoxicity occurred in two and one patients, respectively, while grade 1 and 2 cytokine release syndrome was observed in three patients each.
Among the 12 patients treated to date, the overall response rate was 81% at day 28, Dr. Hari said, noting that of 6 patients treated at the goal dose of 2.5 x 106 cells/kg, 5 remain in ongoing complete remission.
The median age of patients enrolled in the study was 55 years. Six patients had diffuse large B-cell lymphoma, five had mantle cell lymphoma, and two had chronic lymphocytic leukemia. All but one patient underwent fludarabine/cyclophosphamide lymphodepletion prior to receiving the inpatient CAR T-cell infusions, given over the course of 2 days.
Dr. Hari specifically highlighted the mantle cell lymphoma patient subset, noting that four out of five patients were in complete remission at day 28, and remained in ongoing complete remission at times ranging from 1 to 16 months.
With a set manufacturing time of 14 days, production was successful in all 12 patients, and 10 were able to receive fresh product, while 3 received cryopreserved product due to illness-related delays and a holiday, according to the investigators.
“The time to actual delivery of CAR T cell in the patient is actually shortened dramatically,” Dr. Hari said. “We hope to get it down to day 10.”
Local manufacturing can also reduce some costs associated with CAR T-cell production, such as shipping and courier costs, he added.
Taken together, these findings suggest that locally manufactured anti-CD19/CD20 CAR T cells could improve clinical outcomes for patients with relapsed and refractory B-cell NHL, with efficiency through point-of-care delivery, Dr. Hari concluded.
Further studies are planned to evaluate the efficacy of the product and to investigate the mechanism of relapse or progression in patients who experience treatment failure, he said.
Dr. Hari reported disclosures related to Juno, Kite, Spectrum, Janssen, Takeda, Celgene, and BMS. Several study coauthors reported that they were employed by Lentigen Technology, a Miltenyi Biotec Company.
The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
SOURCE: Shah NN et al. TCT 2019, Abstract 80.
REPORTING FROM TCT 2019
AlloBMT should be option for older adults with hematologic malignancies
HOUSTON – Allogeneic blood and marrow transplantation (alloBMT) with posttransplant cyclophosphamide (PTCy) is relatively safe and feasible in septuagenarians with hematologic malignancies and should be considered in this population, findings from a review of 108 cases suggest.
The main difference in outcomes in older versus younger patients is a higher – but still low – rate of nonrelapse mortality (NRM) that appears to be due in part to age-related causes, Philip Hollingsworth Imus, MD, of Johns Hopkins University and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, reported at the Transplantation & Cellular Therapy Meetings.
Overall survival (OS) among the 108 consecutive patients over age 70 years who underwent alloBMT at Johns Hopkins from Jan. 1, 2009, through March 31, 2018, was 64% at 1 year and 43% at 3 years, and progression-free survival (PFS) was 50% at 1 year and 32% at 3 years, Dr. Imus said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
NRM, especially later NRM, however, seemed to be increased, he said, noting that 6-month NRM was acceptable at 14%, but at 1 and 3 years it was 20% and 29%, respectively.
“In contrast to younger patients, [hematopoietic cell transplantation–specific comorbidity index] did not seem to predict NRM in our cohort,” he said.
Early causes of NRM were “in keeping with what we typically see,” and included pneumonia, sepsis, and a few cases of cytokine release syndrome, but later causes of NRM included some that are commonly seen in older patients without hematologic malignancies, such as secondary malignancies, dementia, falls, and cerebrovascular accidents, he said.
Based on frailty research suggesting that weight loss and gain may contribute to outcomes in older patients, Dr. Imus and his colleagues also performed a landmark analysis looking at weight change at 6 months versus pretreatment weight, and found that OS was 31 months in those with greater than the median loss of 4.4 kg, compared with 79 months in those who maintained or regained weight and who therefore had less than the median weight loss at 6 months.
The patients in this series had a median age of 72 years, and the refined disease risk index was low in 9% of patients, intermediate in 77%, and high or very high in 13%. All received nonmyeloablative (NMA) conditioning, PTCy and mycophenolate mofetil prophylaxis from day 5 to day 35, and either tacrolimus and sirolimus from day 5 to day 60-180.
The graft source was bone marrow in 75% of patients.
Engraftment in this population was acceptable and similar to that seen in younger patients; there were seven graft failures, with most occurring in patients who received bone marrow grafts, Dr. Imus said.
The incidence of severe, acute, and chronic graft-versus-host disease was about 10% for each, and was also similar to what is seen in younger patients, he noted.
The findings are of interest because many hematologic malignancies in septuagenarians are associated with very poor survival in the absence of alloBMT. It has only been in recent years that advances in NMA conditioning and haploidentical donor use have made alloBMT more available to older patients, he explained.
With increasing numbers of patients over age 70 years being offered the therapy – about 10% of adult alloBMT recipients at Johns Hopkins are over age 70 now – it was of interest to look at these outcomes, he said, adding that the findings demonstrate that hematologic malignancies in older patients are curable with alloBMT.
“Patients should not be denied therapy based on age alone,” Dr. Imus said, noting that in an effort to address the finding of increased graft failures in those receiving bone marrow grafts at Johns Hopkins, peripheral blood is now being used in certain cases.
“Nonrelapse mortality continues to be a major challenge in this group. It rivals relapse for poor outcomes, especially for late nonrelapse mortality,” he said, concluding that prospective studies looking at NRM are warranted.
Dr. Imus reported having no financial disclosures.
SOURCE: Imus P et al. TCT 2019, Abstract 42.
HOUSTON – Allogeneic blood and marrow transplantation (alloBMT) with posttransplant cyclophosphamide (PTCy) is relatively safe and feasible in septuagenarians with hematologic malignancies and should be considered in this population, findings from a review of 108 cases suggest.
The main difference in outcomes in older versus younger patients is a higher – but still low – rate of nonrelapse mortality (NRM) that appears to be due in part to age-related causes, Philip Hollingsworth Imus, MD, of Johns Hopkins University and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, reported at the Transplantation & Cellular Therapy Meetings.
Overall survival (OS) among the 108 consecutive patients over age 70 years who underwent alloBMT at Johns Hopkins from Jan. 1, 2009, through March 31, 2018, was 64% at 1 year and 43% at 3 years, and progression-free survival (PFS) was 50% at 1 year and 32% at 3 years, Dr. Imus said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
NRM, especially later NRM, however, seemed to be increased, he said, noting that 6-month NRM was acceptable at 14%, but at 1 and 3 years it was 20% and 29%, respectively.
“In contrast to younger patients, [hematopoietic cell transplantation–specific comorbidity index] did not seem to predict NRM in our cohort,” he said.
Early causes of NRM were “in keeping with what we typically see,” and included pneumonia, sepsis, and a few cases of cytokine release syndrome, but later causes of NRM included some that are commonly seen in older patients without hematologic malignancies, such as secondary malignancies, dementia, falls, and cerebrovascular accidents, he said.
Based on frailty research suggesting that weight loss and gain may contribute to outcomes in older patients, Dr. Imus and his colleagues also performed a landmark analysis looking at weight change at 6 months versus pretreatment weight, and found that OS was 31 months in those with greater than the median loss of 4.4 kg, compared with 79 months in those who maintained or regained weight and who therefore had less than the median weight loss at 6 months.
The patients in this series had a median age of 72 years, and the refined disease risk index was low in 9% of patients, intermediate in 77%, and high or very high in 13%. All received nonmyeloablative (NMA) conditioning, PTCy and mycophenolate mofetil prophylaxis from day 5 to day 35, and either tacrolimus and sirolimus from day 5 to day 60-180.
The graft source was bone marrow in 75% of patients.
Engraftment in this population was acceptable and similar to that seen in younger patients; there were seven graft failures, with most occurring in patients who received bone marrow grafts, Dr. Imus said.
The incidence of severe, acute, and chronic graft-versus-host disease was about 10% for each, and was also similar to what is seen in younger patients, he noted.
The findings are of interest because many hematologic malignancies in septuagenarians are associated with very poor survival in the absence of alloBMT. It has only been in recent years that advances in NMA conditioning and haploidentical donor use have made alloBMT more available to older patients, he explained.
With increasing numbers of patients over age 70 years being offered the therapy – about 10% of adult alloBMT recipients at Johns Hopkins are over age 70 now – it was of interest to look at these outcomes, he said, adding that the findings demonstrate that hematologic malignancies in older patients are curable with alloBMT.
“Patients should not be denied therapy based on age alone,” Dr. Imus said, noting that in an effort to address the finding of increased graft failures in those receiving bone marrow grafts at Johns Hopkins, peripheral blood is now being used in certain cases.
“Nonrelapse mortality continues to be a major challenge in this group. It rivals relapse for poor outcomes, especially for late nonrelapse mortality,” he said, concluding that prospective studies looking at NRM are warranted.
Dr. Imus reported having no financial disclosures.
SOURCE: Imus P et al. TCT 2019, Abstract 42.
HOUSTON – Allogeneic blood and marrow transplantation (alloBMT) with posttransplant cyclophosphamide (PTCy) is relatively safe and feasible in septuagenarians with hematologic malignancies and should be considered in this population, findings from a review of 108 cases suggest.
The main difference in outcomes in older versus younger patients is a higher – but still low – rate of nonrelapse mortality (NRM) that appears to be due in part to age-related causes, Philip Hollingsworth Imus, MD, of Johns Hopkins University and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, reported at the Transplantation & Cellular Therapy Meetings.
Overall survival (OS) among the 108 consecutive patients over age 70 years who underwent alloBMT at Johns Hopkins from Jan. 1, 2009, through March 31, 2018, was 64% at 1 year and 43% at 3 years, and progression-free survival (PFS) was 50% at 1 year and 32% at 3 years, Dr. Imus said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
NRM, especially later NRM, however, seemed to be increased, he said, noting that 6-month NRM was acceptable at 14%, but at 1 and 3 years it was 20% and 29%, respectively.
“In contrast to younger patients, [hematopoietic cell transplantation–specific comorbidity index] did not seem to predict NRM in our cohort,” he said.
Early causes of NRM were “in keeping with what we typically see,” and included pneumonia, sepsis, and a few cases of cytokine release syndrome, but later causes of NRM included some that are commonly seen in older patients without hematologic malignancies, such as secondary malignancies, dementia, falls, and cerebrovascular accidents, he said.
Based on frailty research suggesting that weight loss and gain may contribute to outcomes in older patients, Dr. Imus and his colleagues also performed a landmark analysis looking at weight change at 6 months versus pretreatment weight, and found that OS was 31 months in those with greater than the median loss of 4.4 kg, compared with 79 months in those who maintained or regained weight and who therefore had less than the median weight loss at 6 months.
The patients in this series had a median age of 72 years, and the refined disease risk index was low in 9% of patients, intermediate in 77%, and high or very high in 13%. All received nonmyeloablative (NMA) conditioning, PTCy and mycophenolate mofetil prophylaxis from day 5 to day 35, and either tacrolimus and sirolimus from day 5 to day 60-180.
The graft source was bone marrow in 75% of patients.
Engraftment in this population was acceptable and similar to that seen in younger patients; there were seven graft failures, with most occurring in patients who received bone marrow grafts, Dr. Imus said.
The incidence of severe, acute, and chronic graft-versus-host disease was about 10% for each, and was also similar to what is seen in younger patients, he noted.
The findings are of interest because many hematologic malignancies in septuagenarians are associated with very poor survival in the absence of alloBMT. It has only been in recent years that advances in NMA conditioning and haploidentical donor use have made alloBMT more available to older patients, he explained.
With increasing numbers of patients over age 70 years being offered the therapy – about 10% of adult alloBMT recipients at Johns Hopkins are over age 70 now – it was of interest to look at these outcomes, he said, adding that the findings demonstrate that hematologic malignancies in older patients are curable with alloBMT.
“Patients should not be denied therapy based on age alone,” Dr. Imus said, noting that in an effort to address the finding of increased graft failures in those receiving bone marrow grafts at Johns Hopkins, peripheral blood is now being used in certain cases.
“Nonrelapse mortality continues to be a major challenge in this group. It rivals relapse for poor outcomes, especially for late nonrelapse mortality,” he said, concluding that prospective studies looking at NRM are warranted.
Dr. Imus reported having no financial disclosures.
SOURCE: Imus P et al. TCT 2019, Abstract 42.
REPORTING FROM TCT 2019
MRD negativity linked to survival in MM after auto-HCT
HOUSTON – Minimal residual disease (MRD) negativity by multiparameter flow cytometry was linked to survival benefit in multiple myeloma patients undergoing autologous transplantation, according to results of the first U.S.-based study evaluating this endpoint as part of a national randomized clinical trial.
MRD-negative status was prognostic for improved progression-free survival at all time points measured over the course of 1 year post transplant, in this ancillary study of patients in the randomized, 3-arm STAMiNA trial.
Moreover, there was an overall survival benefit for MRD-negative status at 1 year post transplant, investigator Theresa A. Hahn, PhD, of Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., reported at the Transplantation & Cellular Therapy Meetings.
There was no significant difference in rate of conversion to MRD negativity in the arms of the trial, which evaluated several different upfront approaches to autologous hematopoietic stem cell transplantation (HCT).
Assessments of MRD beyond 1 year post transplant may be valuable in future trials, Dr. Hahn said.
“Trials are needed incorporating MRD as an endpoint for treatment decisions to augment, change, or discontinue therapy,” she added.
Results of the ancillary study known as PRIMeR (Prognostic Immunophenotyping for Myeloma Response) included 445 patients from STAMiNA who underwent MRD assessment at baseline, prior to maintenance, and at 1 year post transplantation.
As part of the overall STAMiNA trial, they were randomized to single autologous hematopoietic cell transplantation (HCT); autologous HCT followed by a second autologous HCT (tandem autologous HCT); or single autologous HCT followed by four cycles of consolidation with lenalidomide, bortezomib, and dexamethasone (RVD). All three arms continued on lenalidomide maintenance after those interventions.
Overall results of the STAMiNA trial, previously reported, showed no significant differences in progression-free survival or overall survival among the three transplant strategies (J Clin Oncol. 2019 Jan 17. doi: 10.1200/JCO.18.00685).
In this PRIMeR substudy, by contrast, progression-free survival was significantly increased for patients who were MRD negative at all three time points measured, Dr. Hahn reported, while overall survival was significantly improved based on MRD status measured at the 1-year time point.
The rate of MRD negativity did not differ significantly between arms at baseline or premaintenance time points, Dr. Hahn said. Those rates were 42%, 47%, and 40%, respectively, for the single transplant, tandem transplant, and single transplant plus consolidation arms, while the premaintenance MRD negativity rates were 77%, 83%, and 76%.
At 1 year, MRD negativity rates were significantly different between arms, but only in the intent-to-treat analysis.
Most of the difference was due to an increased rate of MRD negativity in the tandem-transplant arm, compared to a single auto-transplant. However, about 30% of patients in the tandem transplant arm did not receive the therapy, so in the analysis by actual treatment received, the rates of MRD negativity were 81% for single transplant, 90% for tandem transplant, and 85% for single transplant plus consolidation (P = 0.2).
Dr. Hahn said she and her colleagues will be updating their analysis of the PRIMeR study to assess the predictive value of MRD status in patients who were negative at all time points evaluated, versus those who converted to MRD negativity at the 1-year analysis.
The MRD assessments used in this trial have been incorporated into the recently completed BMT CTN 1401 trial and the ongoing BMT CTN 1302 study of allogeneic HCT plus ixazomib in high-risk myeloma, she added.
Dr. Hahn reported research funding from Celgene and the National Institutes of Health.
The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
SOURCE: Hahn TE et al. TCT 2019, Abstract 6.
HOUSTON – Minimal residual disease (MRD) negativity by multiparameter flow cytometry was linked to survival benefit in multiple myeloma patients undergoing autologous transplantation, according to results of the first U.S.-based study evaluating this endpoint as part of a national randomized clinical trial.
MRD-negative status was prognostic for improved progression-free survival at all time points measured over the course of 1 year post transplant, in this ancillary study of patients in the randomized, 3-arm STAMiNA trial.
Moreover, there was an overall survival benefit for MRD-negative status at 1 year post transplant, investigator Theresa A. Hahn, PhD, of Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., reported at the Transplantation & Cellular Therapy Meetings.
There was no significant difference in rate of conversion to MRD negativity in the arms of the trial, which evaluated several different upfront approaches to autologous hematopoietic stem cell transplantation (HCT).
Assessments of MRD beyond 1 year post transplant may be valuable in future trials, Dr. Hahn said.
“Trials are needed incorporating MRD as an endpoint for treatment decisions to augment, change, or discontinue therapy,” she added.
Results of the ancillary study known as PRIMeR (Prognostic Immunophenotyping for Myeloma Response) included 445 patients from STAMiNA who underwent MRD assessment at baseline, prior to maintenance, and at 1 year post transplantation.
As part of the overall STAMiNA trial, they were randomized to single autologous hematopoietic cell transplantation (HCT); autologous HCT followed by a second autologous HCT (tandem autologous HCT); or single autologous HCT followed by four cycles of consolidation with lenalidomide, bortezomib, and dexamethasone (RVD). All three arms continued on lenalidomide maintenance after those interventions.
Overall results of the STAMiNA trial, previously reported, showed no significant differences in progression-free survival or overall survival among the three transplant strategies (J Clin Oncol. 2019 Jan 17. doi: 10.1200/JCO.18.00685).
In this PRIMeR substudy, by contrast, progression-free survival was significantly increased for patients who were MRD negative at all three time points measured, Dr. Hahn reported, while overall survival was significantly improved based on MRD status measured at the 1-year time point.
The rate of MRD negativity did not differ significantly between arms at baseline or premaintenance time points, Dr. Hahn said. Those rates were 42%, 47%, and 40%, respectively, for the single transplant, tandem transplant, and single transplant plus consolidation arms, while the premaintenance MRD negativity rates were 77%, 83%, and 76%.
At 1 year, MRD negativity rates were significantly different between arms, but only in the intent-to-treat analysis.
Most of the difference was due to an increased rate of MRD negativity in the tandem-transplant arm, compared to a single auto-transplant. However, about 30% of patients in the tandem transplant arm did not receive the therapy, so in the analysis by actual treatment received, the rates of MRD negativity were 81% for single transplant, 90% for tandem transplant, and 85% for single transplant plus consolidation (P = 0.2).
Dr. Hahn said she and her colleagues will be updating their analysis of the PRIMeR study to assess the predictive value of MRD status in patients who were negative at all time points evaluated, versus those who converted to MRD negativity at the 1-year analysis.
The MRD assessments used in this trial have been incorporated into the recently completed BMT CTN 1401 trial and the ongoing BMT CTN 1302 study of allogeneic HCT plus ixazomib in high-risk myeloma, she added.
Dr. Hahn reported research funding from Celgene and the National Institutes of Health.
The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
SOURCE: Hahn TE et al. TCT 2019, Abstract 6.
HOUSTON – Minimal residual disease (MRD) negativity by multiparameter flow cytometry was linked to survival benefit in multiple myeloma patients undergoing autologous transplantation, according to results of the first U.S.-based study evaluating this endpoint as part of a national randomized clinical trial.
MRD-negative status was prognostic for improved progression-free survival at all time points measured over the course of 1 year post transplant, in this ancillary study of patients in the randomized, 3-arm STAMiNA trial.
Moreover, there was an overall survival benefit for MRD-negative status at 1 year post transplant, investigator Theresa A. Hahn, PhD, of Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., reported at the Transplantation & Cellular Therapy Meetings.
There was no significant difference in rate of conversion to MRD negativity in the arms of the trial, which evaluated several different upfront approaches to autologous hematopoietic stem cell transplantation (HCT).
Assessments of MRD beyond 1 year post transplant may be valuable in future trials, Dr. Hahn said.
“Trials are needed incorporating MRD as an endpoint for treatment decisions to augment, change, or discontinue therapy,” she added.
Results of the ancillary study known as PRIMeR (Prognostic Immunophenotyping for Myeloma Response) included 445 patients from STAMiNA who underwent MRD assessment at baseline, prior to maintenance, and at 1 year post transplantation.
As part of the overall STAMiNA trial, they were randomized to single autologous hematopoietic cell transplantation (HCT); autologous HCT followed by a second autologous HCT (tandem autologous HCT); or single autologous HCT followed by four cycles of consolidation with lenalidomide, bortezomib, and dexamethasone (RVD). All three arms continued on lenalidomide maintenance after those interventions.
Overall results of the STAMiNA trial, previously reported, showed no significant differences in progression-free survival or overall survival among the three transplant strategies (J Clin Oncol. 2019 Jan 17. doi: 10.1200/JCO.18.00685).
In this PRIMeR substudy, by contrast, progression-free survival was significantly increased for patients who were MRD negative at all three time points measured, Dr. Hahn reported, while overall survival was significantly improved based on MRD status measured at the 1-year time point.
The rate of MRD negativity did not differ significantly between arms at baseline or premaintenance time points, Dr. Hahn said. Those rates were 42%, 47%, and 40%, respectively, for the single transplant, tandem transplant, and single transplant plus consolidation arms, while the premaintenance MRD negativity rates were 77%, 83%, and 76%.
At 1 year, MRD negativity rates were significantly different between arms, but only in the intent-to-treat analysis.
Most of the difference was due to an increased rate of MRD negativity in the tandem-transplant arm, compared to a single auto-transplant. However, about 30% of patients in the tandem transplant arm did not receive the therapy, so in the analysis by actual treatment received, the rates of MRD negativity were 81% for single transplant, 90% for tandem transplant, and 85% for single transplant plus consolidation (P = 0.2).
Dr. Hahn said she and her colleagues will be updating their analysis of the PRIMeR study to assess the predictive value of MRD status in patients who were negative at all time points evaluated, versus those who converted to MRD negativity at the 1-year analysis.
The MRD assessments used in this trial have been incorporated into the recently completed BMT CTN 1401 trial and the ongoing BMT CTN 1302 study of allogeneic HCT plus ixazomib in high-risk myeloma, she added.
Dr. Hahn reported research funding from Celgene and the National Institutes of Health.
The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
SOURCE: Hahn TE et al. TCT 2019, Abstract 6.
REPORTING FROM TCT 2019
Anti-GM-CSF antibody reduced CAR T-cell toxicity
HOUSTON – Neutralizing granulocyte-macrophage colony-stimulating factor (GM-CSF) may be an effective strategy not only to manage toxicities associated with chimeric antigen receptor (CAR) T-cell therapy, but also to enhance CAR-T cell function, an investigator reported at the Transplantation & Cellular Therapy Meetings.
The GM-CSF targeted monoclonal antibody lenzilumab reduced neurotoxicity and cytokine release syndrome (CRS) related to CD19-targeted CAR T-cell therapy in a patient-derived xenograft model, said investigator Rosalie M. Sterner, an MD-PhD student in the department of immunology at Mayo Clinic, Rochester, Minn.
Other investigations showed that neutralizing or knocking out GM-CSF enhanced the antitumor functions of the CAR T cells, Ms. Sterner said in a podium presentation at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
“GM-CSF blockade does not impair CAR T-cell effector function, and in fact, enhances CAR T-cell effector functions in certain models, and actually can help to ameliorate CAR T-cell associated toxicities,” Ms. Sterner said.
Based on these early findings, the investigators have designed a phase 2 clinical trial to see if lenzilumab can prevent CAR T cell-related toxicities in patients with diffuse large B-cell lymphoma.
GM-CSF, a cytokine produced by T cells and myeloid cells, is the most statistically significantly elevated serum marker in patients with severe neurotoxicity related to CAR T-cell therapy, Ms. Sterner told attendees.
Investigations have shown that the combination of lenzilumab plus CD19-targeted T-cell therapy did not impair CAR T-cell function in vivo or in vitro, she said.
In other studies, they investigated the impact of GM-CSF neutralization in mice engrafted with primary acute lymphocytic leukemia (ALL) blasts and treated with high doses of CD19 CAR T-cells, lenzilumab, and a murine GM-CSF blocking antibody to neutralize the mouse GM-CSF. That strategy prevented weight loss, decreased myeloid cytokines, reduced cerebral edema, and enhanced disease control, Ms. Sterner said.
Investigators also reported on CD19 CAR T-cells with reduced GM-CSF secretion due to CRISPR/Cas9 gene editing of the GM-CSF gene during the CAR T-cell manufacturing process. Xenograft model results showed a slight enhancement of disease control for those GM-CSF knockout CAR T cells versus standard CAR T cells.
More details of the investigations were recently published in Blood (2019;133:697-709).
Taken together, the investigations highlight GM-CSF inhibition as a novel approach to reducing neurotoxicity and CRS that may also enhance CAR T-cell effector functions, Ms. Sterner said.
Ms. Sterner reported having no financial disclosures related to her presentation.
SOURCE: Sterner R et al. TCT 2019, Abstract 5.
HOUSTON – Neutralizing granulocyte-macrophage colony-stimulating factor (GM-CSF) may be an effective strategy not only to manage toxicities associated with chimeric antigen receptor (CAR) T-cell therapy, but also to enhance CAR-T cell function, an investigator reported at the Transplantation & Cellular Therapy Meetings.
The GM-CSF targeted monoclonal antibody lenzilumab reduced neurotoxicity and cytokine release syndrome (CRS) related to CD19-targeted CAR T-cell therapy in a patient-derived xenograft model, said investigator Rosalie M. Sterner, an MD-PhD student in the department of immunology at Mayo Clinic, Rochester, Minn.
Other investigations showed that neutralizing or knocking out GM-CSF enhanced the antitumor functions of the CAR T cells, Ms. Sterner said in a podium presentation at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
“GM-CSF blockade does not impair CAR T-cell effector function, and in fact, enhances CAR T-cell effector functions in certain models, and actually can help to ameliorate CAR T-cell associated toxicities,” Ms. Sterner said.
Based on these early findings, the investigators have designed a phase 2 clinical trial to see if lenzilumab can prevent CAR T cell-related toxicities in patients with diffuse large B-cell lymphoma.
GM-CSF, a cytokine produced by T cells and myeloid cells, is the most statistically significantly elevated serum marker in patients with severe neurotoxicity related to CAR T-cell therapy, Ms. Sterner told attendees.
Investigations have shown that the combination of lenzilumab plus CD19-targeted T-cell therapy did not impair CAR T-cell function in vivo or in vitro, she said.
In other studies, they investigated the impact of GM-CSF neutralization in mice engrafted with primary acute lymphocytic leukemia (ALL) blasts and treated with high doses of CD19 CAR T-cells, lenzilumab, and a murine GM-CSF blocking antibody to neutralize the mouse GM-CSF. That strategy prevented weight loss, decreased myeloid cytokines, reduced cerebral edema, and enhanced disease control, Ms. Sterner said.
Investigators also reported on CD19 CAR T-cells with reduced GM-CSF secretion due to CRISPR/Cas9 gene editing of the GM-CSF gene during the CAR T-cell manufacturing process. Xenograft model results showed a slight enhancement of disease control for those GM-CSF knockout CAR T cells versus standard CAR T cells.
More details of the investigations were recently published in Blood (2019;133:697-709).
Taken together, the investigations highlight GM-CSF inhibition as a novel approach to reducing neurotoxicity and CRS that may also enhance CAR T-cell effector functions, Ms. Sterner said.
Ms. Sterner reported having no financial disclosures related to her presentation.
SOURCE: Sterner R et al. TCT 2019, Abstract 5.
HOUSTON – Neutralizing granulocyte-macrophage colony-stimulating factor (GM-CSF) may be an effective strategy not only to manage toxicities associated with chimeric antigen receptor (CAR) T-cell therapy, but also to enhance CAR-T cell function, an investigator reported at the Transplantation & Cellular Therapy Meetings.
The GM-CSF targeted monoclonal antibody lenzilumab reduced neurotoxicity and cytokine release syndrome (CRS) related to CD19-targeted CAR T-cell therapy in a patient-derived xenograft model, said investigator Rosalie M. Sterner, an MD-PhD student in the department of immunology at Mayo Clinic, Rochester, Minn.
Other investigations showed that neutralizing or knocking out GM-CSF enhanced the antitumor functions of the CAR T cells, Ms. Sterner said in a podium presentation at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
“GM-CSF blockade does not impair CAR T-cell effector function, and in fact, enhances CAR T-cell effector functions in certain models, and actually can help to ameliorate CAR T-cell associated toxicities,” Ms. Sterner said.
Based on these early findings, the investigators have designed a phase 2 clinical trial to see if lenzilumab can prevent CAR T cell-related toxicities in patients with diffuse large B-cell lymphoma.
GM-CSF, a cytokine produced by T cells and myeloid cells, is the most statistically significantly elevated serum marker in patients with severe neurotoxicity related to CAR T-cell therapy, Ms. Sterner told attendees.
Investigations have shown that the combination of lenzilumab plus CD19-targeted T-cell therapy did not impair CAR T-cell function in vivo or in vitro, she said.
In other studies, they investigated the impact of GM-CSF neutralization in mice engrafted with primary acute lymphocytic leukemia (ALL) blasts and treated with high doses of CD19 CAR T-cells, lenzilumab, and a murine GM-CSF blocking antibody to neutralize the mouse GM-CSF. That strategy prevented weight loss, decreased myeloid cytokines, reduced cerebral edema, and enhanced disease control, Ms. Sterner said.
Investigators also reported on CD19 CAR T-cells with reduced GM-CSF secretion due to CRISPR/Cas9 gene editing of the GM-CSF gene during the CAR T-cell manufacturing process. Xenograft model results showed a slight enhancement of disease control for those GM-CSF knockout CAR T cells versus standard CAR T cells.
More details of the investigations were recently published in Blood (2019;133:697-709).
Taken together, the investigations highlight GM-CSF inhibition as a novel approach to reducing neurotoxicity and CRS that may also enhance CAR T-cell effector functions, Ms. Sterner said.
Ms. Sterner reported having no financial disclosures related to her presentation.
SOURCE: Sterner R et al. TCT 2019, Abstract 5.
REPORTING FROM TCT 2019
Treosulfan may become standard in allo-HCT for AML/MDS
HOUSTON – A treosulfan-based conditioning regimen could become standard prior to allogeneic transplant in elderly or comorbid patients with acute myeloid leukemia or myelodysplastic syndromes, according to the lead investigator in a phase 3 trial.
The treosulfan/fludarabine myeloablative conditioning regimen had noninferior event-free survival, compared with a reduced-intensity busulfan-based regimen in the large, randomized trial that included elderly patients and those with multiple comorbidities, said researcher Dietrich Wilhelm Beelen, MD, PhD.
The experimental regimen was superior to busulfan in overall survival, nonrelapse mortality, and complete donor chimerism in the trial, added Dr. Beelen, who is with the department of bone marrow transplantation at the West German Cancer Center, University Hospital of Essen, Germany.
“The study results point to a potential benefit of the treosulfan/fludarabine regimen, while the early safety profile, engraftment kinetics, acute or chronic graft-versus-host-disease (GvHD), and the relapse risk of both regimens appear comparable,” Dr. Beelen said at the Transplantation & Cellular Therapy Meetings.
Allogeneic hematopoietic cell transplantation (HCT) is challenging in elderly and comorbid patients, who have an increased risk of nonrelapse mortality with standard myeloablative regimens, according to Dr. Beelen, who presented results on behalf of investigators from the international MC-FludT.14/L Study Group.
Their phase 3 randomized trial included patients who were 50-70 years of age, or who had a Hematopoietic Cell Transplantation Comorbidity Index of 2 or greater. The final analysis included 551 patients (352 with AML and 199 with MDS).
The primary endpoint of the study was event-free survival at 2 years. That endpoint comprised relapse/progression of disease, graft failure, or death.
Patient enrollment was terminated early the MC-FludT.14/L study following an interim analysis that investigators said “clearly demonstrated” the noninferiority of the treosulfan/fludarabine regimen versus the reduced intensity busulfan/fludarabine regimen.
In the final analysis, event-free survival at 2 years was about 14.5 percentage points higher in the treosulfan group, at 65.7% versus 51.2% (P = .0000001), Dr. Beelen reported at the meeting.
A number of other secondary endpoints also favored treosulfan/fludarabine over busulfan, including overall survival (P = .0037), nonrelapse mortality (P = .0343), and survival free of chronic GvHD or relapse (P = .0030).
These results help establish the new treosulfan/fludarabine regimen as a “relatively well-tolerable and effective preparative regimen” in elderly or comorbid AML/MDS patients, Dr. Beelen said.
However, treosulfan has not been authorized for use in allogeneic HCT conditioning regimens, and so should be considered experimental in this setting, he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
Dr. Beelen reported honoraria, travel support, and trial documentation support provided by medac GmbH, which sponsored the trial.
SOURCE: Beelen DW et al. TCT 2019, Abstract 4.
HOUSTON – A treosulfan-based conditioning regimen could become standard prior to allogeneic transplant in elderly or comorbid patients with acute myeloid leukemia or myelodysplastic syndromes, according to the lead investigator in a phase 3 trial.
The treosulfan/fludarabine myeloablative conditioning regimen had noninferior event-free survival, compared with a reduced-intensity busulfan-based regimen in the large, randomized trial that included elderly patients and those with multiple comorbidities, said researcher Dietrich Wilhelm Beelen, MD, PhD.
The experimental regimen was superior to busulfan in overall survival, nonrelapse mortality, and complete donor chimerism in the trial, added Dr. Beelen, who is with the department of bone marrow transplantation at the West German Cancer Center, University Hospital of Essen, Germany.
“The study results point to a potential benefit of the treosulfan/fludarabine regimen, while the early safety profile, engraftment kinetics, acute or chronic graft-versus-host-disease (GvHD), and the relapse risk of both regimens appear comparable,” Dr. Beelen said at the Transplantation & Cellular Therapy Meetings.
Allogeneic hematopoietic cell transplantation (HCT) is challenging in elderly and comorbid patients, who have an increased risk of nonrelapse mortality with standard myeloablative regimens, according to Dr. Beelen, who presented results on behalf of investigators from the international MC-FludT.14/L Study Group.
Their phase 3 randomized trial included patients who were 50-70 years of age, or who had a Hematopoietic Cell Transplantation Comorbidity Index of 2 or greater. The final analysis included 551 patients (352 with AML and 199 with MDS).
The primary endpoint of the study was event-free survival at 2 years. That endpoint comprised relapse/progression of disease, graft failure, or death.
Patient enrollment was terminated early the MC-FludT.14/L study following an interim analysis that investigators said “clearly demonstrated” the noninferiority of the treosulfan/fludarabine regimen versus the reduced intensity busulfan/fludarabine regimen.
In the final analysis, event-free survival at 2 years was about 14.5 percentage points higher in the treosulfan group, at 65.7% versus 51.2% (P = .0000001), Dr. Beelen reported at the meeting.
A number of other secondary endpoints also favored treosulfan/fludarabine over busulfan, including overall survival (P = .0037), nonrelapse mortality (P = .0343), and survival free of chronic GvHD or relapse (P = .0030).
These results help establish the new treosulfan/fludarabine regimen as a “relatively well-tolerable and effective preparative regimen” in elderly or comorbid AML/MDS patients, Dr. Beelen said.
However, treosulfan has not been authorized for use in allogeneic HCT conditioning regimens, and so should be considered experimental in this setting, he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
Dr. Beelen reported honoraria, travel support, and trial documentation support provided by medac GmbH, which sponsored the trial.
SOURCE: Beelen DW et al. TCT 2019, Abstract 4.
HOUSTON – A treosulfan-based conditioning regimen could become standard prior to allogeneic transplant in elderly or comorbid patients with acute myeloid leukemia or myelodysplastic syndromes, according to the lead investigator in a phase 3 trial.
The treosulfan/fludarabine myeloablative conditioning regimen had noninferior event-free survival, compared with a reduced-intensity busulfan-based regimen in the large, randomized trial that included elderly patients and those with multiple comorbidities, said researcher Dietrich Wilhelm Beelen, MD, PhD.
The experimental regimen was superior to busulfan in overall survival, nonrelapse mortality, and complete donor chimerism in the trial, added Dr. Beelen, who is with the department of bone marrow transplantation at the West German Cancer Center, University Hospital of Essen, Germany.
“The study results point to a potential benefit of the treosulfan/fludarabine regimen, while the early safety profile, engraftment kinetics, acute or chronic graft-versus-host-disease (GvHD), and the relapse risk of both regimens appear comparable,” Dr. Beelen said at the Transplantation & Cellular Therapy Meetings.
Allogeneic hematopoietic cell transplantation (HCT) is challenging in elderly and comorbid patients, who have an increased risk of nonrelapse mortality with standard myeloablative regimens, according to Dr. Beelen, who presented results on behalf of investigators from the international MC-FludT.14/L Study Group.
Their phase 3 randomized trial included patients who were 50-70 years of age, or who had a Hematopoietic Cell Transplantation Comorbidity Index of 2 or greater. The final analysis included 551 patients (352 with AML and 199 with MDS).
The primary endpoint of the study was event-free survival at 2 years. That endpoint comprised relapse/progression of disease, graft failure, or death.
Patient enrollment was terminated early the MC-FludT.14/L study following an interim analysis that investigators said “clearly demonstrated” the noninferiority of the treosulfan/fludarabine regimen versus the reduced intensity busulfan/fludarabine regimen.
In the final analysis, event-free survival at 2 years was about 14.5 percentage points higher in the treosulfan group, at 65.7% versus 51.2% (P = .0000001), Dr. Beelen reported at the meeting.
A number of other secondary endpoints also favored treosulfan/fludarabine over busulfan, including overall survival (P = .0037), nonrelapse mortality (P = .0343), and survival free of chronic GvHD or relapse (P = .0030).
These results help establish the new treosulfan/fludarabine regimen as a “relatively well-tolerable and effective preparative regimen” in elderly or comorbid AML/MDS patients, Dr. Beelen said.
However, treosulfan has not been authorized for use in allogeneic HCT conditioning regimens, and so should be considered experimental in this setting, he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
Dr. Beelen reported honoraria, travel support, and trial documentation support provided by medac GmbH, which sponsored the trial.
SOURCE: Beelen DW et al. TCT 2019, Abstract 4.
REPORTING FROM TCT 2019
Ultrasound method predicts liver complications in pediatric transplant
HOUSTON – An ultrasound method for assessing liver stiffness might be useful for predicting which pediatric patients will develop a life-threatening complication of hematopoietic stem cell transplantation.
Shear wave elastography values predicted severe hepatic sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) at least 4 days before standard diagnostic criteria in most patients treated in a small, prospective, two-center study, Sherwin S. Chan, MD, PhD, said at the Transplantation & Cellular Therapy Meetings.
Early identification of SOS/VOD using elastography could be beneficial in light of data showing that timing is critical in the administration of defibrotide, a treatment recommended for severe and very severe patients, according to Dr. Chan, vice chair of radiology for the University of Missouri at Kansas City.
“If you’re able to initiate it early, you can really increase day 100 survival,” Dr. Chan said in an oral presentation.
The data presented included 54 pediatric patients undergoing transplantation at one of two institutions.
At one site, the patients underwent shear wave elastography evaluation 10 days before the conditioning regimen began, and again at 5 and 14 days after the transplant. At the other site, patients with suspected SOS/VOD were enrolled and underwent elastography every other day for up to 10 exams.
Those are very different imaging protocols, Dr. Chan acknowledged in his presentation, noting that the studies started independently and data were pooled as investigators at the two institutions became aware of one another’s work.
A total of 16 patients, or 30%, developed SOS/VOD, Dr. Chan reported. Of those 16 cases, 12 (75%) were severe or very severe by the recent European Society for Blood and Marrow Transplantation (EBMT) criteria.
Increased shear wave elastography velocity was the best predictor of severe SOS/VOD, according to Dr. Chan, with a cutoff value of 1.65 m/s being 92% sensitive and 67% specific for severe SOS/VOD.
That threshold was passed at least 4 days before severe grading or death in 9 out of the 12 severe cases, he added.
Accordingly, a prospective, multicenter trial has been initiated at a number of U.S. centers to investigate whether the findings of this study are generalizable to other patient populations, Dr. Chan said at the meeting held by the American Society of Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At this meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy.
That prospective, multicenter trial is supported by Jazz Pharmaceuticals, according to Dr. Chan, who reported consulting with Jazz Pharmaceuticals in his disclosure statement.
SOURCE: Chan SS et al. TCT 2019, Abstract 55.
HOUSTON – An ultrasound method for assessing liver stiffness might be useful for predicting which pediatric patients will develop a life-threatening complication of hematopoietic stem cell transplantation.
Shear wave elastography values predicted severe hepatic sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) at least 4 days before standard diagnostic criteria in most patients treated in a small, prospective, two-center study, Sherwin S. Chan, MD, PhD, said at the Transplantation & Cellular Therapy Meetings.
Early identification of SOS/VOD using elastography could be beneficial in light of data showing that timing is critical in the administration of defibrotide, a treatment recommended for severe and very severe patients, according to Dr. Chan, vice chair of radiology for the University of Missouri at Kansas City.
“If you’re able to initiate it early, you can really increase day 100 survival,” Dr. Chan said in an oral presentation.
The data presented included 54 pediatric patients undergoing transplantation at one of two institutions.
At one site, the patients underwent shear wave elastography evaluation 10 days before the conditioning regimen began, and again at 5 and 14 days after the transplant. At the other site, patients with suspected SOS/VOD were enrolled and underwent elastography every other day for up to 10 exams.
Those are very different imaging protocols, Dr. Chan acknowledged in his presentation, noting that the studies started independently and data were pooled as investigators at the two institutions became aware of one another’s work.
A total of 16 patients, or 30%, developed SOS/VOD, Dr. Chan reported. Of those 16 cases, 12 (75%) were severe or very severe by the recent European Society for Blood and Marrow Transplantation (EBMT) criteria.
Increased shear wave elastography velocity was the best predictor of severe SOS/VOD, according to Dr. Chan, with a cutoff value of 1.65 m/s being 92% sensitive and 67% specific for severe SOS/VOD.
That threshold was passed at least 4 days before severe grading or death in 9 out of the 12 severe cases, he added.
Accordingly, a prospective, multicenter trial has been initiated at a number of U.S. centers to investigate whether the findings of this study are generalizable to other patient populations, Dr. Chan said at the meeting held by the American Society of Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At this meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy.
That prospective, multicenter trial is supported by Jazz Pharmaceuticals, according to Dr. Chan, who reported consulting with Jazz Pharmaceuticals in his disclosure statement.
SOURCE: Chan SS et al. TCT 2019, Abstract 55.
HOUSTON – An ultrasound method for assessing liver stiffness might be useful for predicting which pediatric patients will develop a life-threatening complication of hematopoietic stem cell transplantation.
Shear wave elastography values predicted severe hepatic sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) at least 4 days before standard diagnostic criteria in most patients treated in a small, prospective, two-center study, Sherwin S. Chan, MD, PhD, said at the Transplantation & Cellular Therapy Meetings.
Early identification of SOS/VOD using elastography could be beneficial in light of data showing that timing is critical in the administration of defibrotide, a treatment recommended for severe and very severe patients, according to Dr. Chan, vice chair of radiology for the University of Missouri at Kansas City.
“If you’re able to initiate it early, you can really increase day 100 survival,” Dr. Chan said in an oral presentation.
The data presented included 54 pediatric patients undergoing transplantation at one of two institutions.
At one site, the patients underwent shear wave elastography evaluation 10 days before the conditioning regimen began, and again at 5 and 14 days after the transplant. At the other site, patients with suspected SOS/VOD were enrolled and underwent elastography every other day for up to 10 exams.
Those are very different imaging protocols, Dr. Chan acknowledged in his presentation, noting that the studies started independently and data were pooled as investigators at the two institutions became aware of one another’s work.
A total of 16 patients, or 30%, developed SOS/VOD, Dr. Chan reported. Of those 16 cases, 12 (75%) were severe or very severe by the recent European Society for Blood and Marrow Transplantation (EBMT) criteria.
Increased shear wave elastography velocity was the best predictor of severe SOS/VOD, according to Dr. Chan, with a cutoff value of 1.65 m/s being 92% sensitive and 67% specific for severe SOS/VOD.
That threshold was passed at least 4 days before severe grading or death in 9 out of the 12 severe cases, he added.
Accordingly, a prospective, multicenter trial has been initiated at a number of U.S. centers to investigate whether the findings of this study are generalizable to other patient populations, Dr. Chan said at the meeting held by the American Society of Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At this meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy.
That prospective, multicenter trial is supported by Jazz Pharmaceuticals, according to Dr. Chan, who reported consulting with Jazz Pharmaceuticals in his disclosure statement.
SOURCE: Chan SS et al. TCT 2019, Abstract 55.
REPORTING FROM TCT 2019