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Leo I. Gordon, MD, FACP
Leo I. Gordon, MD, FACP
Posted: Tuesday, June 28, 2022
On June 24, the U.S. Food and Drug Administration (FDA) approved lisocabtagene maraleucel (Breyanzi) for adults with large B-cell lymphoma (LBCL) who have refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age. The CD19-directed chimeric antigen receptor (CAR) T-cell therapy is not indicated for the treatment of patients with primary central nervous system lymphoma.
Efficacy of lisocabtagene maraleucel was evaluated in TRANSFORM, a randomized, open-label, multicenter trial in adults with primary refractory LBCL or relapse within 12 months of achieving complete response to first-line therapy. Patients had not yet received treatment of relapsed or refractory lymphoma and were potential candidates for autologous HSCT. A total of 184 patients were randomly assigned 1:1 to receive a single infusion of lisocabtagene maraleucel following fludarabine and cyclophosphamide lymphodepleting chemotherapy or second-line standard therapy, consisting of three cycles of chemoimmunotherapy followed by high-dose therapy and autologous HSCT in those who attained a complete response or a partial response.
The primary efficacy measure was event-free survival (EFS), as determined by an independent review committee. EFS was significantly longer with lisocabtagene maraleucel, with a hazard ratio (HR) of 0.34 (P < .0001). The estimated 1-year EFS was 45% with lisocabtagene maraleucel and 24% with standard therapy. The estimated median EFS was 10.1 months and 2.3 months, respectively. The independent review committee–assessed progression-free survival was also significantly longer with lisocabtagene maraleucel, with a HR of 0.41 (P = .0001).
The FDA approved lisocabtagene maraleucel with a Risk Evaluation and Mitigation Strategy because of the risk of fatal or life-threatening cytokine-release syndrome and neurologic toxicities. In studies of lisocabtagene maraleucel as second-line therapy for LBCL, cytokine-release syndrome occurred in 45% of patients (≥ grade 3, 1.3%), and neurologic toxicities occurred in 27% (grade 3, 7%).
The recommended lisocabtagene maraleucel dose for second-line therapy is 90 to 110 × 106 CAR-positive T cells, with a 1:1 ratio of CD4 and CD8 components.
U.S. Food and Drug Administration
