The FDA has approved lisocabtagene maraleucel (Breyanzi®, Juno Therapeutics) for patients with relapsed/refractory large B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DCBLC transformed from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal B-cell lymphoma, and grade 3B follicular lymphoma, who have progressive disease following at least two prior lines of systemic therapy. Lisocabtagene maraleucel is not indicated for patients with primary central nervous system lymphoma.
"Lisocabtagene maraleucel is an autologous, CD19–directed chimeric antigen receptor (CAR) T-cell product," wrote the investigators of the TRANSCEND trial (NCT02631044), led by first author Jeremy S. Abramson, MD, Associate Professor of Medicine at Harvard Medical School and Director of the Lymphoma Program at Massachusetts General Hospital, in their September publication in The Lancet. "We aimed to assess the activity and safety of lisocabtagene maraleucel in patients with relapsed or refractory large B-cell lymphomas."
TRANSCEND, the single-arm, open-label trial on which the approval was based, enrolled 344 adult patients with relapsed/refractory large B-cell lymphomas who developed progressive disease following two or more lines of systemic therapy. All patients received lymphodepleting chemotherapy and underwent leukapheresis for the manufacture of CAR-positive T cells prior to being assigned to receive lisocabtagene maraleucel in a dose of 50x106, 100x106, or 150x106 CAR-positive T cells, all of which were administered as a sequential infusion at equal target doses. The study's primary end points were objective response, adverse events, and dose-limiting toxicities.
Among 192 evaluable patients, lisocabtagene maraleucel produced an overall response rate of 73% and a complete response rate of 54%, with a median time to first response of 1 month. In 104 patients who experienced a complete response, remissions lasting at least 6 months occurred in 65% of patients, and remissions lasting at least 9 months occurred in 62% of patients. The estimated median duration of response was 1.4 months in those who experienced a partial response and was not reached in those who had a complete response.
Grade 3 or higher adverse events included prolonged cytopenias (31%), infections (19%), neurologic toxicity (12%), and cytokine release syndrome (4%). Any-grade cytokine release syndrome and neurologic events were experienced by 46% and 35% of patients, respectively, with fatal neurologic toxicity in three patients. Dose-limiting toxicities occurred in 6% of patients. Lisocabtagene maraleucel is approved with a Risk Evaluation and Mitigation Strategy (REMS) to manage the risks of cytokine release syndrome and neurological toxicities.
"Use of lisocabtagene maraleucel resulted in a high objective response rate, with a low incidence of grade 3 or worse cytokine release syndrome and neurological events in patients with relapsed or refractory large B-cell lymphomas, including those with diverse histological subtypes and high-risk features," concluded Dr. Abramson and colleagues.
The recommended regimen of lisocabtagene maraleucel is a single dose of 50 to 110 x106 CAR-positive T cells with a 1:1 ratio of CD4 and CD8 components, administered intravenously following lymphodepletion with fludarabine and cyclophosphamide.
For More Information
Abramson JS, Palomba ML, Gordon LI, et al (2020). Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet, 396(10254):839-852. DOI:10.1016/S0140-6736(20)31366-0
US Food & Drug Administration (2021). FDA approves lisocabtagene maraleucel for relapsed or refractory large B-cell lymphoma. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-lisocabtagene-maraleucel-relapsed-or-refractory-large-b-cell-lymphoma
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