FDA Approval of Lisocabtagene Maraleucel for Patients With R/R Mantle Cell Lymphoma

On May 30th, 2024, the U.S. Food and Drug Administration (FDA) approved lisocabtagene maraleucel for adult patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) who have received at least 2 prior lines of systemic therapy, including a Bruton’s tyrosine kinase (BTK) inhibitor.

This approval was based on results from the open-label, multicenter, single-arm TRANSCEND-MCL trial, which included adult patients with R/R MCL who had received at least 2 prior lines of therapy including a BTK inhibitor, an alkylating agent, and an anti-CD20 agent. The main efficacy outcome measure was overall response rate (ORR), which was defined as the percentage of patients with the best overall response (BOR) of either complete response (CR) or partial response (PR) after lisocabtagene maraleucel infusion. This was determined by an independent review committee (IRC) using 2014 Lugano classification.

The trial included 68 patients who received a single dose of lisocabtagene maraleucel 2 to 7 days following the completion of lymphodepleting chemotherapy (fludarabine 30 mg/m²/day and cyclophosphamide 300 mg/m²/day concurrently for 3 days).

Efficacy analysis was determined among patients with MCL who received at least 2 prior lines of therapy including a BTK inhibitor, had PET-positive disease at study baseline or after bridging therapy, received conforming product in the intended dose range, and had at least 6 months of follow-up from the date of first response. Additionally, eligibility included those with an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or less, prior autologous and/or allogeneic hematopoietic stem cell transplantation (HSCT), and secondary central nervous system (CNS) lymphoma involvement.

Study results demonstrated an ORR of 85.3% (95% confidence interval [CI], 74.6 to 92.7) and a CRR of 67.6% (95% CI, 55.2 to 78.5). After a median follow-up of 22.2 months (95% CI, 16.7 to 22.8), the median duration of response (DOR)  was 13.3 months (95% CI, 6.0 to 23.3).

Safety measurements showed that the most common non-laboratory adverse reactions (≥ 20%) were cytokine release syndrome (CRS), fatigue, musculoskeletal pain, encephalopathy, edema, headache, and decreased appetite. Additionally, the FDA has approved lisocabtagene maraleucel with a Risk Evaluation and Mitigation Strategy because of the risk of fatal or life-threatening CRS and neurologic toxicities.

Source:

FDA approves lisocabtagene maraleucel for relapsed or refractory mantle cell lymphoma. U.S. Food and Drug Administration. Published online May 30, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lisocabtagene-maraleucel-relapsed-or-refractory-mantle-cell-lymphoma