Bristol Myers Squibb Presents Data Evaluating Potential of Liso-cel Across Leukemia and Lymphomas at ASH 2020
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- Published on Tuesday, 08 December 2020 10:51
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Liso-cel elicited high overall response rates in relapsed or refractory chronic lymphocytic leukemia and small lymphocytic lymphoma both as monotherapy and in combination with ibrutinib, and rapid, deep and durable responses were observed with the longer-term follow-up monotherapy treated cohort in TRANSCEND CLL 0041,2
Preliminary results from TRANSCEND NHL 001 cohort evaluating liso-cel in relapsed or refractory mantle cell lymphoma showed high response rates3
Initial results from OUTREACH study for patients with relapsed or refractory large B-cell lymphoma treated with liso-cel in the inpatient and outpatient settings also presented4
PRINCETON, NJ, USA I December 07, 2020 I Bristol Myers Squibb (NYSE: BMY) today announced data from multiple studies evaluating lisocabtagene maraleucel (liso-cel), an investigational CD19-directed chimeric antigen receptor (CAR) T cell therapy, in relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), in relapsed or refractory mantle cell lymphoma (MCL), and in relapsed or refractory large B-cell lymphoma (LBCL) were presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition. The data include longer-term follow-up from the Phase 1 TRANSCEND CLL 004 study in a cohort of patients with relapsed or refractory CLL and SLL treated with liso-cel as monotherapy and initial results from the combination cohort with ibrutinib, and safety and preliminary efficacy results from TRANSCEND NHL 001 in the cohort of patients with relapsed or refractory MCL treated with liso-cel. Additionally, initial results from the OUTREACH study evaluating outcomes of treatment with liso-cel for patients with relapsed or refractory LBCL across inpatient and outpatient settings were presented.
“In our mission to transform patients’ lives through science, we have established a diverse and comprehensive development program to understand the potential of liso-cel across both aggressive and indolent hematologic malignancies and sites of care,” said Noah Berkowitz, M.D., Ph.D., senior vice president, Global Clinical Development, Hematology, Bristol Myers Squibb. “In addition, we continue to advance our cell therapy research to inform potential combination strategies with our CAR T cell therapies to optimize treatment outcomes for patients in need.”
Liso-cel in Combination with Ibrutinib and as Monotherapy in CLL/SLL: TRANSCEND CLL 004
In the Phase 1/2 TRANSCEND CLL 004 study, patients with relapsed or refractory CLL and SLL were enrolled in a cohort receiving liso-cel in combination with ibrutinib (Presentation #544). Nineteen patients started or continued ibrutinib treatment for >90 days at enrollment and were evaluated for safety and efficacy following liso-cel treatment.
Seventy-four percent of patients experienced any grade cytokine release syndrome (CRS) with one Grade 3 event. Median time to onset of CRS was 6.5 days (1-13) and median duration of CRS was 6 days (3-13). Any grade neurologic events (NEs) occurred in 32% of patients with three Grade 3 events. Median time to onset of NEs was 8 days (5-12) and median duration of NEs was 6.5 days (1-8).1
With median follow-up of 10 months, liso-cel in combination with ibrutinib demonstrated high rates of response with 18 patients (95%) deriving an overall response, and 12 (63%) achieving a complete response. All responses were achieved by Day 30 following liso-cel treatment and among 18 patients with >6 months of follow-up, 89% maintained or improved their response from Day 30. Of 19 patients evaluable for minimal residual disease (MRD), 17 (89%) achieved undetectable MRD (uMRD) in blood by flow cytometry and 15 (79%) in bone marrow by next-generation sequencing (both with sensitivity 104).1
In a separate cohort of the Phase 1/2 TRANSCEND CLL 004 study, patients with relapsed or refractory CLL, including 83% of patients with high-risk disease, and patients who had progressed on prior therapy with ibrutinib, were enrolled to receive liso-cel as a monotherapy (Presentation #546). At median follow-up of 24 months, 23 patients were evaluable for safety and 22 patients were evaluable for efficacy.
In the 23 patients evaluated for safety, the safety profile for liso-cel was consistent with the known safety profile of liso-cel with no new late or delayed adverse events of concern emerging with longer follow-up. Seventy-four percent of patients experienced any grade CRS, with Grade >3 CRS occurring in 9% of patients. Median time to onset of CRS was three days (1-10) and median duration of CRS was 12 days (2-50). Any grade NEs occurred in 39% of patients, with 22% of patients experiencing Grade >3 NEs. Median time to onset of NEs was four days (2-21) and median duration of NEs was 20.5 days (6-50).2
Among the 22 patients evaluable for efficacy, the overall response rate was 82% (18/22). Complete responses were seen in 46% (10/22) of patients. By Day 30, 68% of patients (n=15) responded to therapy, and 27% had a deepening of response. At 12 months, 50% of patients remained in response and all seven patients who completed the 24-month follow-up maintained their response. The median duration of response was not reached (95% CI: 4.8 – NR) at median follow-up of 24 months and median progression-free survival was 18 months (95% CI: 3.0 – NR).2
“Patients with relapsed or refractory chronic lymphocytic leukemia and small lymphocytic lymphoma are often faced with a difficult treatment journey and many changes in therapy due to relapse,” said William G. Wierda, M.D., Ph.D., executive medical director and professor, Department of Leukemia, Division of Cancer Medicine at the University of Texas MD Anderson Cancer Center. “Results from TRANSCEND CLL 004 underscore the potential of liso-cel to deliver rapid, deep and durable responses as a monotherapy in heavily pretreated patients with difficult-to-treat disease and the potential of using liso-cel in combination with ibrutinib to provide high rates of overall response with a very manageable safety profile to address a significant unmet need for this disease.”
Safety and Efficacy of Liso-cel in Relapsed or Refractory MCL: TRANSCEND NHL 001
In the TRANSCEND NHL 001 study cohort of patients with relapsed or refractory MCL, including many with highly proliferative disease, 32 patients received liso-cel across dose levels of 50 x 106 CAR positive T cells and 100 x 106 CAR positive T cells (Presentation #118).
Sixteen patients (50%) experienced any grade CRS, including one Grade >3 event. Median time to CRS onset and resolution was six days (2‒10) and four days (2-9), respectively. Eleven patients (34%) experienced any grade NEs, all of which occurred in those who received the higher dose level, including four Grade >3 NEs. Median time to NE onset and resolution was eight days (2-25) and four days (1-27), respectively.3
Preliminary efficacy results showed that treatment with liso-cel resulted in high response rates with 84% of patients responding to treatment and 66% of patients achieving a complete response (CR). Overall, the median time to first complete or partial response was less than one month (0.95; range 0.9-2.0). Median duration of response was not reached with a median follow-up of 3.9 months (0.0-21.3).3
“Mantle cell lymphoma is an aggressive type of non-Hodgkin lymphoma and many patients relapse after initial therapies with limited remaining treatment options,” said M. Lia Palomba, M.D., Lymphoma Service and Center for Cellular Therapeutics, Memorial Sloan Kettering Cancer Center. “Initial results of liso-cel in MCL from TRANSCEND NHL 001 demonstrate the potential of this CAR T cell therapy to provide patients with high rates of response, representing a potentially important treatment option for these patients.”
Initial Results from the OUTREACH Study of Liso-cel in Relapsed or Refractory Large B-Cell Lymphoma (LBCL) Across Sites of Care
In the Phase 2 OUTREACH study, adults with relapsed or refractory LBCL were treated with liso-cel in the inpatient and outpatient settings at nonuniversity centers (Presentation #1196). The primary endpoint was incidence of Grade >3 CRS based on the Lee grading system, NEs, prolonged cytopenias through day 29 and infections. Secondary endpoints included safety and overall response rate (ORR).
Based on initial results from 46 patients treated with liso-cel (inpatient n=16; outpatient n=30) at data cutoff, patients were successfully treated and monitored in the inpatient and outpatient settings. Any grade CRS was reported in six (37.5%) patients treated in the inpatient setting and 13 (43%) patients treated in the outpatient setting, with no Grade >3 events reported. NEs were reported in five (31%) inpatients and nine (30%) outpatients, with one Grade >3 event in the inpatient group and two in the outpatient group. Median time to onset of CRS and NEs, respectively, was 2.5 (1–3) and 10 (3–16) days for inpatients and five (2–9) and nine (6–14) days for outpatients.4
Among efficacy-evaluable patients (n=44), 75% of inpatients achieved an overall response with 50% of patients achieving a complete response (CR), and 79% of outpatients achieved an overall response with 61% achieving a CR.4
Bristol Myers Squibb: Creating a Better Future for People with Cancer
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About Bristol Myers Squibb
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Juno Therapeutics, Inc. is a wholly owned subsidiary of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol Myers Squibb company and Juno Therapeutics, a Bristol Myers Squibb company.
- Wierda, WG., et al. TRANSCEND CLL 004: Phase 1 Cohort of Lisocabtagene Maraleucel (liso-cel) in Combination with Ibrutinib for Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia (CLL/SS). American Society of Hematology Annual Meeting 2020. Presentation #544.
- Siddiqi, T., et al., Updated Follow-Up of Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Treated with Lisocabtagene Maraleucel in the Phase 1 Monotherapy Cohort of TRANSCEND CLL 004, Including High-Risk and Ibrutinib-Treated Patients. American Society of Hematology Annual Meeting 2020. Presentation #546.
- Palomba, ML., et al., Safety and Preliminary Efficacy in Patients with Relapsed/Refractory Mantle Cell Lymphoma Receiving Lisocabtagene Maraleucel in TRANSCEND NHL 001. American Society of Hematology Annual Meeting 2020. Presentation #118.
- Godwin, JE., et al., Outcomes of Treatment with the CAR T Cell Therapy Lisocabtagene Maraleucel in the Nonuniversity Setting: Initial Results from the OUTREACH Study. American Society of Hematology Annual Meeting 2020. Presentation #1196.
SOURCE: Bristol Myers Squibb