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ORLANDO – Lisocabtagene maraleucel (liso-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, has demonstrated manageable toxicity and promising clinical activity in the phase 1 portion of a trial enrolling heavily pretreated patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, according to an investigator.
The overall response rate exceeded 80%, and most patients in response at 6 months had maintained that response at the 9-month mark, said Tanya Siddiqi, MD, of City of Hope National Medical Center, Duarte, Calif.
“Clinical responses were rapid, improved with time, and were deep and durable,” Dr. Siddiqi said at the annual meeting of the American Society of Hematology.
These findings have provided justification for conducting the phase 2 portion of the study, which is currently enrolling at the higher of two dose levels evaluated in phase 1, she added.
Dr. Siddiqi reported on a total of 23 patients enrolled in the study, known as TRANSCEND CLL 004. All patients had relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and had received at least two prior therapies, including ibrutinib, while about one-third had failed venetoclax as well.
The median patient age was 66 years, and 83% had high-risk features, according to Dr. Siddiqi, who said patients had received a median of five prior lines of therapy.
Nine patients were treated at dose level 1, or 50 x 106 CAR+ T cells, while 14 were treated at dose level 2, or 100 x 106 CAR+ T cells. Two patients experienced grade 3 or 4 dose-limiting toxicities at the second level, including hypertension in one patient, and encephalopathy, muscle weakness, and tumor lysis syndrome (TLS) in the other.
Cytokine release syndrome (CRS) occurred in 17 patients, though only two cases reached grade 3. Neurologic adverse events were seen in nine patients, of which five were grade 3 or 4.
Partial or complete responses were noted in 81.5%, or 18 of 22 evaluable patients, including 10 (45.5%) who had complete remission. In the subset of nine patients who had failed both ibrutinib and venetoclax, that overall response rate was a “very impressive” 89% (eight of nine patients), said Dr. Siddiqi, including 67% complete remissions (six patients).
Undetectable minimal residual disease (MRD) was reported in 65% and 75% of patients, depending on the method used to evaluate it.
About two-thirds of the patients had responses by day 30 evaluation, and responses deepened over time in about one-quarter, according to Dr. Siddiqi. Of 12 patients with a response at 6 months, 10 (83%) were still in response at 9 months, and 8 patients have been in response for 12 months or longer, she reported.
Neurologic adverse events seen in the CLL/SLL patients in this study were associated with higher lymph node tumor burden, and increased levels of interleukin(IL)-16 or tumor necrosis factor (TNF), according to further analysis presented by Dr. Siddiqi.
That raises the possibility that IL-16 or TNF may be a “good predictive biomarker” for neurotoxicity, which seems to be driven at least in part by lymphadenopathy. “If there was a way that we could combine the CAR T-cell with something like a novel agent that can shrink the tumor burden quickly, then maybe we can have even less toxicities with these CAR T cells,” Dr. Siddiqi said.
Dr. Siddiqi reported disclosures related to Kite, TG Therapeutics, Celgene, Janssen, Seattle Genetics, AstraZeneca, PCYC, Juno Therapeutics, and BeiGene.
SOURCE: Siddiqi T et al. ASH 2019, Abstract 503.
ORLANDO – Lisocabtagene maraleucel (liso-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, has demonstrated manageable toxicity and promising clinical activity in the phase 1 portion of a trial enrolling heavily pretreated patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, according to an investigator.
The overall response rate exceeded 80%, and most patients in response at 6 months had maintained that response at the 9-month mark, said Tanya Siddiqi, MD, of City of Hope National Medical Center, Duarte, Calif.
“Clinical responses were rapid, improved with time, and were deep and durable,” Dr. Siddiqi said at the annual meeting of the American Society of Hematology.
These findings have provided justification for conducting the phase 2 portion of the study, which is currently enrolling at the higher of two dose levels evaluated in phase 1, she added.
Dr. Siddiqi reported on a total of 23 patients enrolled in the study, known as TRANSCEND CLL 004. All patients had relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and had received at least two prior therapies, including ibrutinib, while about one-third had failed venetoclax as well.
The median patient age was 66 years, and 83% had high-risk features, according to Dr. Siddiqi, who said patients had received a median of five prior lines of therapy.
Nine patients were treated at dose level 1, or 50 x 106 CAR+ T cells, while 14 were treated at dose level 2, or 100 x 106 CAR+ T cells. Two patients experienced grade 3 or 4 dose-limiting toxicities at the second level, including hypertension in one patient, and encephalopathy, muscle weakness, and tumor lysis syndrome (TLS) in the other.
Cytokine release syndrome (CRS) occurred in 17 patients, though only two cases reached grade 3. Neurologic adverse events were seen in nine patients, of which five were grade 3 or 4.
Partial or complete responses were noted in 81.5%, or 18 of 22 evaluable patients, including 10 (45.5%) who had complete remission. In the subset of nine patients who had failed both ibrutinib and venetoclax, that overall response rate was a “very impressive” 89% (eight of nine patients), said Dr. Siddiqi, including 67% complete remissions (six patients).
Undetectable minimal residual disease (MRD) was reported in 65% and 75% of patients, depending on the method used to evaluate it.
About two-thirds of the patients had responses by day 30 evaluation, and responses deepened over time in about one-quarter, according to Dr. Siddiqi. Of 12 patients with a response at 6 months, 10 (83%) were still in response at 9 months, and 8 patients have been in response for 12 months or longer, she reported.
Neurologic adverse events seen in the CLL/SLL patients in this study were associated with higher lymph node tumor burden, and increased levels of interleukin(IL)-16 or tumor necrosis factor (TNF), according to further analysis presented by Dr. Siddiqi.
That raises the possibility that IL-16 or TNF may be a “good predictive biomarker” for neurotoxicity, which seems to be driven at least in part by lymphadenopathy. “If there was a way that we could combine the CAR T-cell with something like a novel agent that can shrink the tumor burden quickly, then maybe we can have even less toxicities with these CAR T cells,” Dr. Siddiqi said.
Dr. Siddiqi reported disclosures related to Kite, TG Therapeutics, Celgene, Janssen, Seattle Genetics, AstraZeneca, PCYC, Juno Therapeutics, and BeiGene.
SOURCE: Siddiqi T et al. ASH 2019, Abstract 503.
ORLANDO – Lisocabtagene maraleucel (liso-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, has demonstrated manageable toxicity and promising clinical activity in the phase 1 portion of a trial enrolling heavily pretreated patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, according to an investigator.
The overall response rate exceeded 80%, and most patients in response at 6 months had maintained that response at the 9-month mark, said Tanya Siddiqi, MD, of City of Hope National Medical Center, Duarte, Calif.
“Clinical responses were rapid, improved with time, and were deep and durable,” Dr. Siddiqi said at the annual meeting of the American Society of Hematology.
These findings have provided justification for conducting the phase 2 portion of the study, which is currently enrolling at the higher of two dose levels evaluated in phase 1, she added.
Dr. Siddiqi reported on a total of 23 patients enrolled in the study, known as TRANSCEND CLL 004. All patients had relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and had received at least two prior therapies, including ibrutinib, while about one-third had failed venetoclax as well.
The median patient age was 66 years, and 83% had high-risk features, according to Dr. Siddiqi, who said patients had received a median of five prior lines of therapy.
Nine patients were treated at dose level 1, or 50 x 106 CAR+ T cells, while 14 were treated at dose level 2, or 100 x 106 CAR+ T cells. Two patients experienced grade 3 or 4 dose-limiting toxicities at the second level, including hypertension in one patient, and encephalopathy, muscle weakness, and tumor lysis syndrome (TLS) in the other.
Cytokine release syndrome (CRS) occurred in 17 patients, though only two cases reached grade 3. Neurologic adverse events were seen in nine patients, of which five were grade 3 or 4.
Partial or complete responses were noted in 81.5%, or 18 of 22 evaluable patients, including 10 (45.5%) who had complete remission. In the subset of nine patients who had failed both ibrutinib and venetoclax, that overall response rate was a “very impressive” 89% (eight of nine patients), said Dr. Siddiqi, including 67% complete remissions (six patients).
Undetectable minimal residual disease (MRD) was reported in 65% and 75% of patients, depending on the method used to evaluate it.
About two-thirds of the patients had responses by day 30 evaluation, and responses deepened over time in about one-quarter, according to Dr. Siddiqi. Of 12 patients with a response at 6 months, 10 (83%) were still in response at 9 months, and 8 patients have been in response for 12 months or longer, she reported.
Neurologic adverse events seen in the CLL/SLL patients in this study were associated with higher lymph node tumor burden, and increased levels of interleukin(IL)-16 or tumor necrosis factor (TNF), according to further analysis presented by Dr. Siddiqi.
That raises the possibility that IL-16 or TNF may be a “good predictive biomarker” for neurotoxicity, which seems to be driven at least in part by lymphadenopathy. “If there was a way that we could combine the CAR T-cell with something like a novel agent that can shrink the tumor burden quickly, then maybe we can have even less toxicities with these CAR T cells,” Dr. Siddiqi said.
Dr. Siddiqi reported disclosures related to Kite, TG Therapeutics, Celgene, Janssen, Seattle Genetics, AstraZeneca, PCYC, Juno Therapeutics, and BeiGene.
SOURCE: Siddiqi T et al. ASH 2019, Abstract 503.
REPORTING FROM ASH 2019