On June 24, 2022, the FDA approved the CD19-directed chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (Breyanzi; Juno Therapeutics) for the treatment of adults with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal LBCL, and grade 3B follicular lymphoma.
The FDA granted lisocabtagene maraleucel regenerative medicine advanced therapy and breakthrough therapy designations for this indication. This approval includes a Risk Evaluation and Mitigation Strategy program, because of the risk for life-threatening or fatal cytokine release syndrome (CRS) and neurologic adverse events. This CAR T-cell therapy is not approved for primary central nervous system lymphoma.
Lisocabtagene maraleucel was previously approved for various subtypes of relapsed or refractory LBCL after ≥2 lines of systemic therapy.
This new indication was based on the results of the TRANSFORM study, a global, randomized, multicenter, open-label clinical trial in 184 adults with primary refractory LBCL or with relapsed LBCL within 12 months of having a complete response. Patients were randomized in a 1:1 ratio to a single infusion of lisocabtagene maraleucel after lymphodepleting chemotherapy or to second-line therapy with 3 cycles of salvage chemotherapy, followed by high-dose therapy and autologous hematopoietic stem-cell transplant in patients who had a partial or complete response.
The primary efficacy measure was event-free survival (EFS). The results showed a significant improvement in EFS with the CAR T-cell therapy versus the standard of care (hazard ratio [HR], 0.34; 95% confidence interval [CI], 0.22- 0.52; P <.0001); the 1-year EFS rates were 45% and 24%, respectively. The median EFS was 10.1 months with lisocabtagene maraleucel (95% CI, 6.1-nonevaluable) versus 2.3 months with the standard of care (95% CI, 2.2-4.3).
The median progression-free survival was 14.8 months with lisocabtagene maraleucel and 5.7 months with the standard of care (HR, 0.406; P = .0001).
The majority (86%) of the patients who received lisocabtagene maraleucel achieved a partial or complete response, including 66% complete responses, compared with 48% of patients in the standard-of-care arm achieving partial or complete responses, including 39% complete responses.
Lisocabtagene maraleucel had a manageable safety profile, with 49 patients having any-grade CRS, 1 patient having grade 3 CRS, and no grade 4 or 5 CRS reported. In all, 12% of the patients who received the CAR T-cell therapy had any-grade neurologic events, including 4% grade 3 events.