Lisocabtagene Maraleucel Approved for Relapsed or Refractory Mantle Cell Lymphoma

The FDA has granted approval to lisocabtagene maraleucel (Breyanzi®, Juno Therapeutics, Inc.) for adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have received at least two prior lines of systemic therapy, including a Bruton tyrosine kinase inhibitor (BTKi).

Why it matters: “Patients with MCL who experience disease progression after treatment with covalent BTKi have historically poor outcomes with subsequent therapy, including conventional chemotherapy,” wrote Michael Wang, MD, Professor of Lymphoma and Myeloma at MD Anderson Cancer Center, and colleagues, in their published results of the TRANSCEND-NHL-001 trial (NCT02631044), on which approval was based. “Recent studies have demonstrated improved outcomes after treatment with the chimeric antigen receptor (CAR) T-cell therapy brexucabtagene autoleucel; however, treatment-related toxicity is high. As outcomes decline with successive lines of therapy, a continued unmet need exists for treatments that achieve deep and durable responses with a favorable safety profile in patients with relapsed or refractory MCL, including high-risk, aggressive disease.”

What they studied: Efficacy was measured in the phase 1, open-label, single-arm, multicenter trial which included adult patients with relapsed or refractory MCL who had received at least two prior lines of therapy including a BTKi, an alkylating agent, and an anti-CD20 agent. Included in the trial were patients with an Eastern Cooperative Oncology Group (ECOG) performance status of one or less, prior autologous and/or allogeneic hematopoietic stem cell transplantation, and secondary central nervous system lymphoma involvement. Enrollment eligibility included adequate bone marrow function to receive lymphodepleting chemotherapy. There was no prespecified threshold for blood counts.

Two to seven days following the completion of lymphodepleting chemotherapy—consisting of 30 mg/m2/day of fludarabine and 300 mg/m2/day of cyclophosphamide for three concurrent days—patients received a single dose of lisocabtagene maraleucel.

Included in the primary efficacy analysis were 68 patients with MCL who had PET-positive disease at study baseline or after bridging therapy, received conforming product in the intended dose range, and had at least six months of follow-up from the date of first response.

The primary efficacy outcome measured was overall response rate, defined as the percentage of patients with best overall response of either complete response or partial response after lisocabtagene maraleucel infusion, as determined by an independent review committee (IRC) using 2014 Lugano classification. Key secondary efficacy outcomes included complete response rate and duration of response.

What they found: The overall response rate was 85.3%, the complete response rate was 67.5%, and, at a median follow-up of 22.2 months the median duration of response was 13.3 months.

Adverse events: The most common nonlaboratory adverse events experienced in ≥ 20% of those receiving lisocabtagene maraleucel were cytokine release syndrome (CRS), fatigue, musculoskeletal pain, encephalopathy, edema, headache, and decreased appetite. The approval of lisocabtagene maraleucel includes a Risk Evaluation and Mitigation Strategy due to the risk of fatal or life-threatening CRS and neurologic toxicities.

Conclusion: “The current study expands knowledge about CAR T-cell therapy and the clinical landscape of relapsed or refractory MCL in patients with aggressive disease and high-risk features, including those with older age and moderate comorbidities,” concluded Dr. Wang and colleagues. “These results support lisocabtagene maraleucel as a potential new treatment option for relapsed or refractory MCL, particularly in patients for whom limited therapies are available.”

Instructions: The recommended dosage of lisocabtagene maraleucel is 90 to 110 x 106 CAR-positive viable T cells with a 1:1 ratio of CD4 and CD8 components.

For More Information

Wang M, Siddiqi T, Gordon LI, et al (2024). Lisocabtagene maraleucel in relapsed/refractory mantle cell lymphoma: Primary analysis of the mantle cell lymphoma cohort from TRANSCEND NHL 001, a phase I multicenter seamless design study. J Clin Oncol, 42(10):1146-1157. DOI:10.1200/JCO.23.02214

Breyanzi® (lisocabtagene maraleucel) prescribing information (2024). Juno Therapeutics, Inc. Available at: https://www.fda.gov/media/145711/download

Clinicaltrials.gov (2024). Study evaluating the safety and pharmacokinetics of JCAR017 in B-cell non-Hodgkin lymphoma (TRANSCEND-NHL-001). NLM identifier: NCT02631044.

US Food and Drug Administration (2024). FDA approves lisocabtagene maraleucel for relapsed or refractory mantle cell lymphoma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lisocabtagene-maraleucel-relapsed-or-refractory-mantle-cell-lymphoma

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