Liso-cel Meets Primary End Point in Follicular and Mantle Cell Lymphoma Trials

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Bristol Myers Squibb noted that in addition to meeting the ORR end point, both trials also met a key secondary CR rate end point.

Bristol Myers Squibb’s lisocabtagene maraleucel (liso-cel; Breyanzi), a marketed CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy, has met the primary end point of overall response rate (ORR) in 2 separate clinical trials for patients with relapsed/refractory (r/r) follicular lymphoma (FL) (TRANSCEND FL; NCT04245839) and r/r B-cell non-Hodgkin lymphoma (B-NHL) (TRANSCEND NHL 001; NCT02631044), respectively.1 

TRANSCEND FL is a global phase 2 trial which includes patients with FL and marginal zone lymphoma while TRANSCEND NHL 001 is a pivotal phase 1 trial which includes patients with various subtypes of B-NHL: diffuse large B-cell lymphoma, high-grade B-cell lymphoma, primary mediastinal B-cell lymphoma, FL grade 3B, and mantle cell lymphoma (MCL). Both trials are open-label, single-arm, multicenter studies and have secondary end points which include complete response (CR) rate, duration of response, and progression-free survival.

The company noted that in addition to meeting the ORR end point, both trials also met the CR rate end point and no new safety signals were observed in patients with FL and MCL. Bristol Myers Squibb expects to present more detailed results at an upcoming medical conference following a full evaluation of the data.

“For people living with relapsed or refractory follicular lymphoma or mantle cell lymphoma, there are limited treatment options that provide deep and durable responses, especially for patients with high-risk disease,” Anne Kerber, the senior vice president and head of Cell Therapy Development at Bristol Myers Squibb, said in a statement.1 “These continued unmet needs coupled with our deep understanding of lymphoma biology drive us to deliver transformative treatments for patients. We believe these data further confirm Breyanzi’s best-in-class and best-in-disease profile, and underscore the significant progress we are making in bringing the promise of our differentiated CAR T-cell therapy, Breyanzi, to more patients.”

Bristol Myers Squibb previously announced in January 2023 that TRANSCEND CLL 004 (NCT03331198), another clinical trial which is evaluating liso-cel in patients with r/r chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma, met a primary endpoint of "CR rate compared to historical control" in a prespecified subset of patients with r/r CLL refractory to a BTK inhibitor and pretreated with a BCL-2 inhibitor.2 Similarly, no new safety signals were reported at the time. TRANSCEND CLL 004 is a phase 1/2 open-label, single-arm, multicenter study.

“CLL is an incurable disease with complex biology and immune dysregulation that has made the development of T-cell-based therapies that provide deep remission very challenging,” Kerber, said in a January 2023 statement.2 “In a population that has limited options, the TRANSCEND CLL 004 study represents the first multicenter trial evaluating a CAR T-cell therapy in heavily pre-treated patients with relapsed or refractory CLL or SLL, with results showing the potential of Breyanzi as a personalized 1-time treatment approach for patients with this difficult-to-treat disease.”

Liso-cel was originally approved by the FDA in February 2021 for the treatment of adults with r/r diffuse large B-cell lymphomas (LBCL) after at least 2 other types of prior systemic treatments; later on, in June 2022, it received FDA approval for the treatment of patients with LBCL whose disease was r/r to first-line treatment within 12 months and patients with LBCL whose disease was r/r to first-line treatment who are not eligible for hematopoietic stem cell transplant.3,4 The latter approval was based on results from the pivotal phase 3 TRANSFORM clinical trial (NCT03575351). In December 2022, updated data from TRANSFORM demonstrating superiority of liso-cel over standard of care (SOC) treatment in second-line LBCL was presented at the 64th American Society of Hematology (ASH) Annual Meeting, held December 10-12, 2022, in New Orleans, Louisiana, by Jeremy Abramson, MD, the director of the lymphoma program at Massachusetts General Hospital Cencer Center.5 The results reported by Abramson included the finding that second-line liso-cel reduced the risk of an event occurring by 64.4% compared with SOC chemoimmunotherapy induction and autologous stem cell transplant.

REFERENCES
1. Bristol Myers Squibb’s TRANSCEND FL and TRANSCEND NHL 001 studies of Breyanzi (lisocabtagene maraleucel) in relapsed or refractory follicular lymphoma and mantle cell lymphoma meet primary endpoint of overall response rate. News release. Bristol Myers Squibb. May 1, 2023. Accessed May 2, 2023. https://news.bms.com/news/corporate-financial/2023/Bristol-Myers-Squibbs-TRANSCEND-FL-and-TRANSCEND-NHL-001-Studies-of-Breyanzi-lisocabtagene-maraleucelin-Relapsed-or-Refractory-Follicular-Lymphoma-and-Mantle-Cell-Lymphoma-Meet-Primary-Endpoint-of-Overall-Response-Rate/default.aspx
2. Bristol Myers Squibb announces TRANSCEND CLL 004 trial of Breyanzi® (lisocabtagene maraleucel) met primary endpoint of complete response rate in patients with relapsed or refractory chronic lymphocytic leukemia. News release. Bristol Myers Squibb. January 25, 2023. Accessed May 2, 2023. https://www.businesswire.com/news/home/20230125005878/en/Bristol-Myers-Squibb-Announces-TRANSCEND-CLL-004-Trial-of-Breyanzi%C2%AE-lisocabtagene-maraleucel-Met-Primary-Endpoint-of-Complete-Response-Rate-in-Patients-with-Relapsed-or-Refractory-Chronic-Lymphocytic-Leukemia
3. FDA approves new treatment for adults with relapsed or refractory large-B-cell lymphoma. News release. FDA. February 5, 2021. Accessed May 2, 2023. https://www.prnewswire.com/news-releases/fda-approves-new-treatment-for-adults-with-relapsed-or-refractory-large-b-cell-lymphoma-301223275.html
4. U.S. FDA approves Bristol Myers Squibb’s CAR T Cell therapy Breyanzi® for relapsed or refractory large B-cell lymphoma after one prior therapy. News release. Bristol Myers Squibb. June 24, 2022. https://news.bms.com/news/details/2022/US-FDA-Approves-Bristol-Myers-Squibbs-CAR-T-Cell-Therapy-Breyanzifor-Relapsed-or-Refractory-Large-B-cell-Lymphoma-After-One-Prior-Therapy/default.aspx
5. Abramson JS, Solomon SR, Arnason JE, et al. Lisocabtagene maraleucel (liso-cel) versus standard of care (soc) with salvage chemotherapy followed by autologous stem cell transplantation (asct) as second-line (2L) treatment in patients with relapsed or refractory large B-cell lymphoma (LBCL): primary analysis of the randomized, phase 3 Transform study. Blood. 2022;140(suppl 1):1581-1583. doi:10.1182/blood-2022-159702

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