Lisocabtagene Maraleucel Granted Accelerated Approval for Follicular Lymphoma

Alankrita Taneja, MD

The FDA has granted accelerated approval to lisocabtagene maraleucel (Breyanzi®, Juno Therapeutics, Inc.) for adults with relapsed or refractory follicular lymphoma (FL) who have received two or more prior lines of systemic therapy.

Why it matters: “Follicular lymphoma is an indolent subtype of non-Hodgkin lymphoma which has historically been considered incurable. It is characterized by a relapsing and remitting course, with prognosis deteriorating with each relapse. Frequently, the interval between therapies for relapsed disease continues to shorten with every subsequent therapy. Therefore, there is an unmet need for newer therapies in these patients which can prolong treatment-free survival while simultaneously having ease of administration and a tolerable safety profile,” said Alankrita Taneja, MD, a Hematology/Oncology Fellow at Roswell Park Comprehensive Cancer Center, regarding this approval and the trial that led to it: TRANSCEND FL (NCT04245839). “The FDA approval of lisocabtagene maraleucel for patients with relapsed or refractory FL is an important milestone in the FL treatment paradigm, providing the option of a one-time infusion resulting in excellent response rates, a durable remission, and an established safety profile.”

What they studied: Efficacy was studied in the phase 2, single-arm, open-label, multicenter trial which enrolled adults with relapsed or refractory FL after two or more lines of systemic therapy that included an anti-CD20 antibody and an alkylating agent. Ninety-four patients were included in the primary efficacy population. These patients had positron emission tomography (PET)–positive disease at baseline or after bridging therapy, received conforming product in the intended dose range, and had at minimum nine months of follow-up from first response.

Key eligibility criteria included adequate bone marrow functionality to receive lymphodepleting chemotherapy and an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or less. Patients were eligible to receive bridging therapy for disease control following apheresis and prior to lymphodepletion and subsequent administration of lisocabtagene maraleucel.

A single dose of lisocabtagene maraleucel was administered two to seven days after the completion of lymphodepleting chemotherapy, which included three days of 30 mg/m2 per day of fludarabine and 300 mg/m2 per day of cyclophosphamide.

The efficacy end points measured were overall response rate, specified as the percentage of patients with a best response of complete response or partial response after lisocabtagene maraleucel infusion, and duration of response as determined by an independent review committee.

What they found: Following a median follow-up of 16.8 months, overall response rate was 95.7% and the median duration of response was not reached.

Adverse events: The most common nonlaboratory adverse events experienced by ≥20% of patients receiving lisocabtagene maraleucel were cytokine release syndrome (CRS), headache, musculoskeletal pain, fatigue, constipation, and fever. Due to the risk of fatal or life-threatening CRS and neurologic toxicities, the FDA approved lisocabtagene maraleucel with a Risk Evaluation and Mitigation Strategy.

Conclusion: “At this time, there is no standard of care for patients with relapsed or refractory follicular lymphoma who have previously received at least 2 lines of systemic therapy,” concluded Dr. Taneja. “Lisocabtagene maraleucel has previously been FDA-approved for patients with stage 3B FL. However, based on the data presented at the 17th International Conference on Malignant Lymphoma (ICML) from the phase 2 single-arm TRANSCEND FL trial—focusing on FL patients who received chimeric antigen receptor (CAR) T-cell therapy in the third line, referred to as the focused efficacy subset—it has gained accelerated approval for these patients as well. Other CAR-T products including axicabtagene ciloleucel and tisagenlecleucel have also been approved for third-line treatment in FL. In their respective studies, ZUMA-5 showed an overall response rate of 91%, and ELARA showed response rates of 86% in third-line FL. Their complete response rates were 60% and 61%, respectively.”

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

For More Information

Morschhauser F, Dahiya S, Palomba ML, et al (2023). TRANSCEND FL: Phase 2 study primary analysis of lisocabtagene maraleucel as second-line therapy in patients with high-risk relapsed or refractory follicular lymphoma. Presented at the ASH Annual Meeting. Abstract #602. Available at: https://ash.confex.com/ash/2023/webprogram/Paper179474.html

Clinicaltrials.gov (2023). A study to evaluate the efficacy and safety of JCAR017 in adult subjects with relapsed or refractory indolent B-cell non-Hodgkin lymphoma (NHL) (TRANSCEND FL). NLM identifier: NCT04245839.

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

US Food and Drug Administration (2024). FDA grants accelerated approval to lisocabtagene maraleucel for follicular lymphoma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lisocabtagene-maraleucel-follicular-lymphoma

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