Lymphoma treatment for adult patients with relapsed or refractory mantle cell lymphoma (MCL) has been approved by the U.S. Food and Drug Administration (FDA) for lisocabtagene maraleucel (Breyanzi, Juno Therapeutics, Inc.), specifically for those who have received at least two prior lines of systemic therapy, including a Bruton tyrosine kinase inhibitor (BTKi). The efficacy of lisocabtagene maraleucel was assessed in the TRANSCEND-MCL (NCT02631044) trial, an open-label, multicenter, single-arm study involving adult patients with relapsed or refractory mantle cell lymphoma.
To be eligible, patients need to have received at least two prior lines of therapy, including a BTKi, an alkylating agent, and an anti-CD20 agent. The trial also included patients with an ECOG performance status of 1 or less, those who had undergone prior autologous and/or allogeneic hematopoietic stem cell transplantation, and those with secondary central nervous system lymphoma involvement. There was no specified threshold for blood counts; eligibility was determined by the investigator’s assessment of adequate bone marrow function to receive lymphodepletion chemotherapy.
Patients received a single dose of lisocabtagene maraleucel 2 to 7 days after completing lymphodepletion chemotherapy (fludarabine 30 mg/m2/day and cyclophosphamide 300 mg/m2/day concurrently for 3 days). The primary efficacy analysis included 68 patients with mantle cell lymphoma who had received at least two prior lines of therapy including a BTKi, had PET-positive disease at the study baseline or after bridging therapy, received the conforming product in the intended dose range, and had at least 6 months of follow-up from the date of first response.
High Efficacy of Lisocabtagene Maraleucel in Mantle Cell Lymphoma
The main efficacy outcome measure was the overall response rate (ORR), 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, as determined by an independent review committee (IRC) using the 2014 Lugano classification. Additional efficacy measures included the complete response rate (CRR) and the duration of response (DOR), as determined by IRC. The ORR was 85.3% (95% CI: 74.6, 92.7) and the CRR was 67.6% (95% CI: 55.2, 78.5). After a median follow-up of 22.2 months (95% CI: 16.7, 22.8), the median DOR was 13.3 months (95% CI: 6.0, 23.3).
The most common non-laboratory adverse reactions (≥20%) were cytokine release syndrome (CRS), fatigue, musculoskeletal pain, encephalopathy, edema, headache, and decreased appetite. 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 (REMS).
The recommended dose of lisocabtagene maraleucel is 90 to 110 × 10^6 CAR-positive viable T cells with a 1:1 ratio of CD4 and CD8 components. Lisocabtagene maraleucel represents a significant advancement in the treatment of relapsed or refractory mantle cell lymphoma. The TRANSCEND-mantle cell lymphoma trial demonstrated a high overall response rate, with a substantial proportion of patients achieving a complete response. Despite the rigorous safety profile, which includes the potential for severe CRS and neurologic toxicities, the efficacy results highlight the potential for this therapy to provide meaningful clinical benefit to patients with limited treatment options.
A New Hope for Heavily Pretreated Mantle Cell Lymphoma Patients
Patients enrolled in the TRANSCEND-mantle cell lymphoma trial had undergone extensive prior treatments, including BTK inhibitors, which underscores the challenging nature of this patient population. The ability of lisocabtagene maraleucel to induce high response rates in such a refractory group of patients is noteworthy. The study’s findings also emphasize the importance of close monitoring and management of side effects, particularly CRS and neurologic toxicities, to ensure patient safety.
The approval of lisocabtagene maraleucel adds a valuable option to the therapeutic arsenal against mantle cell lymphoma. Its efficacy in heavily pretreated patients suggests it could become a cornerstone treatment for this aggressive lymphoma subtype. The development and approval of such advanced therapies highlight the progress being made in the field of oncology, particularly in leveraging the body’s immune system to fight cancer.
As with any new treatment, real-world data will be crucial to further elucidate the long-term efficacy and safety of lisocabtagene maraleucel. Continued research and post-marketing surveillance will help optimize the use of this therapy, refine patient selection criteria, and improve management strategies for adverse events. Overall, the approval of lisocabtagene maraleucel marks a milestone in the ongoing effort to improve outcomes for patients with mantle cell lymphoma, offering hope for those who have exhausted other treatment options.
Resource: Food and Drug Administration, May 30, 2024
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