FDA Approves Breyanzi for Additional Indication in Large B-Cell Lymphoma

The FDA has approved Breyanzi (lisocabtagene maraleucel) for the treatment of adult patients with large B-cell lymphoma (LBCL) after one prior therapy. Developed by Bristol Myers Squibb, Breyanzi is a CD19-directed chimeric antigen receptor (CAR) T-cell therapy. Breyanzi was previously approved by the FDA for the treatment of adult patients with relapsed or refractory LBCL after two or more lines of systemic therapy.

Lee Greenberger, Ph.D.

“Patients with large B-cell lymphoma whose disease does not respond to or relapses after first-line therapy often face lengthy and intensive cycles of chemotherapy with the goal of proceeding to stem cell transplant,” Lee Greenberger, Ph.D., chief scientific officer of the Leukemia & Lymphoma Society, said in a press release.

Large B-cell lymphoma is a difficult-to-treat and aggressive blood cancer, and up to 40% of patients have disease that is refractory to or relapses after initial therapy. Standard of care is stem cell transplant. But half of patients are not considered candidates for a hematopoietic stem cell transplant due to age and/or comorbidities, and only an estimated 25% of those who are candidates are able to receive a stem cell transplant and experience long-term clinical benefit.

In the pivotal phase 3 TRANSFORM trial, a single infusion of Breyanzi had median event-free survival of 10.1 months vs. 2.3 months for stem cell transplant. Approval was also based on data from the phase 2 PILOT study of a CAR T-cell therapy in patients with primary refractory or relapsed LBCL who are not considered candidates for transplant.

In the TRANSFORM study, the majority of patients achieved a complete response with Breyanzi compared with less than half with standard therapy. In the PILOT study, Breyanzi achieved an overall response rate of 80%, the study’s primary endpoint, and a complete response rate of 54%. Median duration of response was 11.2 months.

Occurrences of cytokine release syndrome and neurologic events were generally low grade and mostly resolved quickly, and without the use of prophylactic steroids. Any-grade cytokine release syndrome was reported in less than half of patients (45%), with grade 3 cytokine release syndrome reported in 1.3% of patients. Any-grade neurologic events were reported in 27%, with grade 3 neurologic events reported in 7% of patients.

Breyanzi is available through a restricted Risk Evaluation and Mitigation Strategy (REMS) program. The REMS program requires Breyanzi to be dispensed in enrolled healthcare facilities with providers who are trained in the management of cytokine release syndrome and neurologic toxicities.