On May 30, the U.S. Food and Drug Administration (FDA) approved the chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (Breyanzi) for adult patients with relapsed or refractory mantle cell lymphoma who have received at least two prior lines of systemic therapy, including a Bruton tyrosine kinase inhibitor.
TRANSCEND NHL 001: Cohort
Efficacy of the therapy was evaluated in the mantle cell lymphoma cohort of TRANSCEND NHL 001, an open-label, multicenter, single-arm trial in adult patients with relapsed or refractory mantle cell lymphoma who had received at least two prior lines of therapy including a Bruton tyrosine kinase inhibitor, an alkylating agent, and an anti-CD20 agent. The trial included patients with an Eastern Cooperative Oncology Group performance status of 1 or less, prior autologous and/or allogeneic hematopoietic stem cell transplantation, and secondary central nervous system lymphoma involvement. There was no prespecified threshold for blood counts; patients were eligible to enroll if they were assessed by the investigator to have adequate bone marrow function to receive lymphodepleting chemotherapy.
Patients received a single dose of lisocabtagene maraleucel 2 to 7 days following the completion of lymphodepleting chemotherapy (fludarabine at 30 mg/m2/d and cyclophosphamide at 300 mg/m2/d concurrently for 3 days). The primary efficacy analysis included a total of 68 patients with mantle cell lymphoma who received at least two prior lines of therapy, including a Bruton tyrosine kinase inhibitor; had positive disease on positron-emission tomography 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.
The main efficacy outcome measure was overall response rate, defined as 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 using 2014 Lugano classification. Other efficacy measures included complete response rate and duration of response as determined by an independent review committee. The overall response rate was 85.3% (95% confidence interval [CI] = 74.6%–92.7%) and the complete response rate was 67.6% (95% CI = 55.2%–78.5%). After a median follow-up of 22.2 months (95% CI = 16.7–22.8 months), the median duration of response was 13.3 months (95% CI = 6.0–23.3 months).
The most common nonlaboratory adverse reactions (occurring in ≥ 20% of patients who received lisocabtagene maraleucel) were cytokine-release syndrome, fatigue, musculoskeletal pain, encephalopathy, edema, headache, and decreased appetite. The FDA approved lisocabtagene maraleucel with a Risk Evaluation and Mitigation Strategy due to the risk of fatal or life-threatening cytokine-release syndrome and neurologic toxicities.
The recommended lisocabtagene maraleucel dose is 90 to 110 × 106 CAR-positive viable T cells with a 1:1 ratio of CD4 and CD8 components.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Priority Review and Orphan Drug designation.
