Breyanzi (lisocabtagene maraleucel; liso-cel) demonstrates clinically meaningful outcomes across a broad range of B-Cell malignancies in new data presented at 2024 ASCO Annual Meeting

The data, presented during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, underscore Breyanzi as a transformative therapy with demonstrated clinically meaningful outcomes across the broadest array of B-cell malignancies. Results from the primary analysis of TRANSCEND FL were simultaneously published in Nature Medicine.

Long-Term Results from TRANSFORM (Abstract #7013).

In the pivotal, global, randomized, multicenter, Phase III TRANSFORM study, 184 patients with primary refractory LBCL or relapsed disease within <12 months after first-line therapy who were eligible for autologous hematopoietic stem cell transplant (hsct) were randomized to receive breyanzi (n="92)" or salvage chemotherapy followed by high-dose chemotherapy and autologous hsct (standard of care, soc; n="92)." with a median follow-up of 33.9 months, breyanzi demonstrated sustained significant clinical benefit with continued improvements in the primary endpoint of event-free survival (efs), and secondary endpoints of progression-free survival (pfs), overall responses and duration of response (dor) compared to soc, consistent with the primary analysis results.

With longer follow-up, EFS with Breyanzi was 29.5 months (95% CI: 9.5-NR) compared to 2.4 months with SoC (95% CI: 2.2-4.9) (HR: 0.375; 95% CI: 0.259-0.542). The 36-month EFS rate with Breyanzi was 45.8% (95% CI: 35.2-56.5) vs. 19.1% (95% CI: 11.0-27.3) for SoC. The overall response rate (ORR) with Breyanzi was 87% (95% CI: 78.3-93.1) with 74% of patients achieving a complete response (CR) (95% CI: 63.7-82.5) vs. a 49% (95% CI: 38.3-59.6) ORR with SoC and a 43% (95% CI: 33.2-54.2) CR rate. DOR was not reached with Breyanzi (95% CI: 16.9-NR) and was 9.1 months with SoC (95% CI:.1-NR) (HR:0.603; 95% CI: 0.364.1.000). Additionally, PFS was not reached with Breyanzi (95% CI: 12.6-NR) vs. 6.2 months (95% CI: 4.3-8.6) for SoC (HR: 0.422; 95% CI: 0.279-0.639). The 36-month PFS rate for Breyanzi was 50.9% (95% CI: 39.9-62.0) and was 26.5% (95% CI: 15.9-37.1) with SoC.

“The long-term data from TRANSFORM builds upon the remarkable results from the primary analysis, with liso-cel continuing to demonstrate deep and durable responses and improved event-free and progression-free survival along with a well-established safety profile,” said Manali Kamdar, M.D., lead investigator of the TRANSFORM study and Associate Professor, Clinical Director of Lymphoma Services, Division of Hematology, Hematologic Malignancies and Stem Cell Transplantation, University of Colorado Cancer Center. “This sustained clinical benefit with a median follow-up of three years is extremely meaningful for patients with relapsed or refractory LBCL, and the results reinforce the value of using a CAR T cell therapy such as liso-cel earlier in the treatment paradigm.”

In the patient-centric trial, which allowed for crossover, 61 patients (66%) in the SoC arm crossed to receive Breyanzi. With longer follow-up, median overall survival (OS) was not reached for either arm, and the 36-month OS rate was numerically higher for Breyanzi (62.8% [95% CI: 52.7-72.9] vs. 51.8% [95% CI: 41.2-62.4]) (HR: 0.757; 95% CI: 0.481-1.191). Additionally, Breyanzi continued to demonstrate a consistent safety profile with no new safety signals observed.

Results from Subgroup Analyses from the MCL Cohort of TRANSCEND NHL 001 (Abstract #7016) and TRANSCEND FL (Abstract #7068): The MCL cohort of TRANSCEND NHL 001 enrolled adults with relapsed or refractory disease after two or more prior lines of therapy, including a BTK inhibitor. In a subgroup analysis reporting outcomes for patients treated with Breyanzi by number of prior lines of therapy and response to prior BTK inhibitor, Breyanzi showed similar efficacy across most subgroups based on overall responses (ORR), complete responses (CR), median duration of response (DOR), progression-free survival (PFS) and overall survival (OS), including in heavily-pretreated patients. The greatest benefit was observed in patients who had received 2-4 prior lines of therapy. Numerically shorter DOR was observed in patients who had received >5 prior lines of therapy and those whose disease was refractory to prior treatment with a BTK inhibitor. The safety profile of Breyanzi was consistent across subgroups and well-tolerated with low rates of severe cytokine release syndrome (CRS) and neurologic events (NE).

The subgroup analysis for TRANSCEND FL in second-line plus relapsed or refractory FL, including second-line high-risk FL, assessed outcomes in patients by bridging therapy status. The primary endpoint of ORR was similar in patients who received bridging therapy (n=45; 93%) and patients who did not receive bridging therapy (n=79; 99%). CR rates were consistently high across both subgroups (93% in bridging therapy and 95% in non-bridging therapy), with all patients who received bridging therapy and responded to Breyanzi treatment achieving CR. Median DOR, PFS, and OS were not reached in either subgroup, with a median follow-up of 18.9 months.

Breyanzi exhibited a consistent safety profile across both groups, with low rates of any-grade CRS (51% in bridging therapy subgroup and 62% in non-bridging therapy subgroup) and any-grade NEs (12% in bridging therapy subgroup and 17% in non-bridging therapy subgroup). Grade 3 CRS (0% vs 1%), NEs (6% vs 0%) and infections (2% vs 7%) were similarly low across subgroups, with no Grade 4 or 5 events.

“The subgroup analyses from the MCL cohort of TRANSCEND NHL 001 and TRANSCEND FL further demonstrate liso-cel's potential as a treatment option for a broad patient population with relapsed or refractory MCL or FL,” said M. Lia Palomba, M.D., TRANSCEND investigator and lymphoma and cell therapy specialist, Memorial Sloan Kettering Cancer Center. “In relapsed or refractory MCL, liso-cel demonstrated clinically meaningful and durable disease control across subgroups, including in earlier lines of treatment where there remains a critical unmet need. Additionally, results from the subgroup analysis from TRANSCEND FL show the consistent clinical benefit of using liso-cel for relapsed or refractory FL with or without prior bridging therapy, with high response rates regardless of bridging status, further expanding the use of liso-cel for these patients.”

See-Morschhauser, F., Dahiya, S., Palomba, M.L. et al. Lisocabtagene maraleucel in follicular lymphoma: the phase II TRANSCEND FL study. Nat Med (2024). https://doi.org/10.1038/s41591-024-02986-9.