On February 5, 2021, the U.S. Food and Drug Administration (FDA) approved lisocabtagene maraleucel (Breyanzi) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B.
Lisocabtagene maraleucel is a CD19-directed chimeric antigen receptor (CAR) T-cell immunotherapy. It consists of autologous T cells that are genetically modified to produce a CAR protein, allowing the T cells to identify and eliminate CD19-expressing normal and malignant cells.
Efficacy was evaluated in TRANSCEND, a single-arm, open-label, multicenter trial that evaluated lisocabtagene maraleucel, preceded by lymphodepleting chemotherapy, in adults with relapsed or refractory large B-cell lymphoma after at least two lines of therapy.
Of the 192 patients evaluable for response, the overall response rate per independent review committee assessment was 73% (95% confidence interval [CI] = 67%–80%), with a complete response rate of 54% (95% CI = 47%–61%). The median time to first response was 1 month. Of the 104 patients who achieved complete response, 65% had remission lasting at least 6 months and 62% had remission lasting at least 9 months. The estimated median duration of response was not reached (95% CI = 16.7 months–not reached) in patients who achieved a complete response. The estimated median duration of response among patients with partial response was 1.4 months (95% CI = 1.1–2.2).
Cytokine release syndrome occurred in 46% of patients (grade 3 or higher = 4%) and neurologic toxicity occurred in 35% (grade 3 or higher = 12%). Three patients had fatal neurologic toxicity. Other grade 3 or higher adverse reactions included infections (19%) and prolonged cytopenias (31%). 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.
The recommended regimen is a single dose containing 50 to 110 × 106 CAR-positive viable T cells with a 1:1 ratio of CD4 and CD8 components, administered by intravenous infusion and preceded by fludarabine and cyclophosphamide for lymphodepletion.
Lisocabtagene maraleucel is not indicated for the treatment of patients with primary central nervous system lymphoma.