Bristol Myers Squibb announces data from three studies evaluating Breyanzi®(lisocabtagene maraleucel; liso-cel), including long-term data with three-year follow-up from the Phase 3 TRANSFORM trial of Breyanzias a second-line treatment in patients with relapsed or refractory large B-cell lymphoma (LBCL), results from a subgroup analysis evaluating the efficacy and safety of Breyanzi by number of prior lines of therapy in the mantle cell lymphoma (MCL) cohort of the TRANSCEND NHL 001 trial, and results from a subgroup analysis assessing the efficacy and safety of Breyanzi based on use of bridging therapy in the TRANSCEND FL trialin relapsed or refractory follicular lymphoma (FL). In the pivotal, global, randomized, multicenter, Phase 3 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.

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.