Bristol Myers Squibb’s Liso-cel Produces Durable Complete Responses in Lymphocytic Leukemia, Lymphoma

Bristol Myers Squibb’s lisocabtagene maraleucel (liso-cel; Breyanzi), a CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy currently marketed in the United States and European Union for large B-cell lymphoma indications, has produced durable complete responses (CRs) among patients with relapses/refractory (r/r) chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) treated in the phase 1/2 TRANSCEND CLL 004 clinical trial (NCT03331198).^1,2 Data from the trial are being presented at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois, by Tanya Siddiqi, MD, the lead investigator and an associate professor in the Division of Lymphoma at City of Hope National Medical Center.

Among the 49 patients who were included in the trial’s primary efficacy analysis set (PEAS) and received dose-level 2 (100x10⁶ CAR T-cells), 9 (18.4%) achieved a CR or CR with incomplete marrow recovery (95% CI, 8.8–32.0; 1-sided P = .0006), meeting the primary end point. Furthermore, at a median follow-up of 19.7 months, the median duration of response (DOR) in the group was 35.3 months (range, 11.01–not reached [NR]). The rate of undetectable minimal residual disease (uMRD) in blood was 63.3% (n = 31; 95% CI [48.3–76.6]) and the uMRD in marrow was 59.2% (n = 29 [95% CI, 44.2–73.0]). The median progression-free survival was 11.9 months (95% CI, 5.72–26.18). It was additionally noted that the overall response rate in this group was 42.9% and not statistically significant (95% CI, 28.8–57.8; 1-sided P = .3931). The PEAS group comprised a subset of the treated patients who experienced disease progression following prior treatment with BTK inhibitor (BTKi) and BCL-2 inhibitor (BCL2i; venetoclax)-based regimens. Bristol Myers Squibb reported that results seen in the trial’s broader population were consistent with results from the PEAS group.

“For people living with relapsed or refractory CLL or SLL after treatment with BTKi and BCL2i-based regimens, there is no standard of care treatment,” Siddiqi said in a statement.² “Achieving deep and lasting remission in this situation is challenging as most patients experience disease progression despite continuous treatment. The durable complete responses observed with liso-cel in the TRANSCEND CLL 004 trial are remarkable and represent a major step in bringing a personalized, T-cell-based treatment approach delivered as a 1-time infusion into clinical practice for a complex and historically incurable disease.”

Among the trial’s safety set, which included all 117 patients treated with liso-cel in the trial, 84.6% of patients experienced cases of cytokine release syndrome (CRS), with 8.5% of patients experiencing grade 3 CRS cases.¹ No grade 4 to 5 CRS cases were reported. Meanwhile, 45.3% of patients experienced neurological events (NEs), with 17.9% of patients experiencing grade 3 NEs and 1 patient (0.9%) experiencing a grade 4 NE. There were no grade 5 NEs reported. Tocilizumab and/or corticosteroids were administered to 69.2% of the patients experiencing CRS and/or NEs. Furthermore, grade 3 or greater infections were reported in 17.1% of patients; grade 3 or greater hypogammaglobulinemia was reported in 15.4% of patients; and grade 3 or greater cases of prolonged cytopenia were reported in 53.8% of patients. A single death deemed related to liso-cel was reported; the death was attributed to hemophagocytic lymphohistiocytosis.

Patients in the safety set had a median age of 65 years (range, 49-82) and 83% of these patients had high-risk features. The number of previous lines of therapy received by the patients ranged from 2 to 12 (median, 5). All of the patients had previously been treated with BTKi. Follow-up for patients in the safety set ranged from 0.4 to 55.6 months (median, 21.1).

“Results from TRANSCEND CLL 004 reinforce our relentless commitment to bringing the potential of CAR T-cell therapy to more patients and transforming the treatment and outcomes for a broad range of hematologic malignancies,” Anne Kerber, the senior vice president and head of Cell Therapy Development at Bristol Myers Squibb, added to the statement.² “Breyanzi has shown clinically meaningful benefit across the broadest array of B-cell malignancies of any CD19-directed CAR T-cell therapy and we remain dedicated to advancing innovative treatments for some of the most difficult-to-treat diseases with high unmet need.”

REFERENCES
1. Siddiqi T, Maloney DG, Kenderian S, et al. Lisocabtagene maraleucel (liso-cel) in R/R chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Primary analysis of TRANSCEND CLL 004. Presented at: the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois. Abstract #7501
2. Bristol Myers Squibb’s Breyanzi (lisocabtagene maraleucel) is first and only CAR T to deliver deep and durable efficacy in pivotal multicenter trial in relapsed or refractory chronic lymphocytic leukemia, based on data presented at ASCO 2023. News release. Bristol Myers Squibb. May 25, 2023. Accessed June 1, 2023. https://news.bms.com/news/corporate-financial/2023/Bristol-Myers-Squibbs-Breyanzi-lisocabtagene-maraleucel-is-First-and-Only-CAR-T-to-Deliver-Deep-and-Durable-Efficacy-in-Pivotal-Multicenter-Trial-in-Relapsed-or-Refractory-Chronic-Lymphocytic-Leukemia-Based-on-Data-Presented-at-ASCO-2023/default.aspx