FDA approves lisocabtagene maraleucel for relapsed or refractory mantle cell lymphoma
Regulatory approval: On May 30, 2024, the FDA approved lisocabtagene maraleucel (Breyanzi) for adult patients with relapsed or refractory mantle cell lymphoma after at least two prior lines of systemic therapy, including a Bruton tyrosine kinase inhibitor. Approval was supported by the single-arm TRANSCEND-MCL trial, in which the primary efficacy population (n=68) had an IRC-assessed ORR of 85.3% and CRR of 67.6%. The product carries a REMS for risks of CRS and neurologic toxicities.
FDA approval (May 30, 2024)
The US Food and Drug Administration (FDA) approved lisocabtagene maraleucel (liso-cel; 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).
Supporting evidence
Efficacy and safety were evaluated in TRANSCEND-MCL (NCT02631044), an open-label, multicenter, single-arm trial in adults with relapsed/refractory MCL who had received ≥2 prior lines including a BTKi, an alkylating agent, and an anti-CD20 agent. Eligible patients included those with ECOG performance status ≤1, prior autologous and/or allogeneic HSCT, and secondary CNS lymphoma involvement.
The primary efficacy analysis included 68 patients with PET-positive disease at baseline or after bridging therapy, who received conforming product in the intended dose range and had ≥6 months of follow-up.
- ORR: 85.3% (95% CI, 74.6–92.7)
- CRR: 67.6% (95% CI, 55.2–78.5)
- Median follow-up: 22.2 months; median DOR: 13.3 months (95% CI, 6.0–23.3)
Safety and REMS
Common nonlaboratory adverse reactions (≥20%) included CRS, fatigue, musculoskeletal pain, encephalopathy, edema, headache, and decreased appetite. FDA approved liso-cel with a Risk Evaluation and Mitigation Strategy (REMS) due to the risk of fatal or life-threatening CRS and neurologic toxicities.
Dosing and review pathway
Recommended dose: 90–110 × 10^6 CAR-positive viable T cells with a 1:1 CD4:CD8 ratio. The application received priority review and orphan drug designation.