FDA grants accelerated approval to lisocabtagene maraleucel for follicular lymphoma

Regulatory approval: On May 15, 2024, the FDA granted accelerated approval to lisocabtagene maraleucel (Breyanzi) for adults with relapsed or refractory follicular lymphoma after ≥2 prior lines of systemic therapy. Approval was supported by the phase 2, single-arm TRANSCEND-FL trial in a primary efficacy population of 94 PET-positive patients. ORR was 95.7% and median DOR was not reached at median follow-up of 16.8 months. A REMS is required for CRS and neurologic toxicities.

FDA accelerated approval: lisocabtagene maraleucel for follicular lymphoma (May 15, 2024)

Type: Regulatory approval (accelerated approval)
Agency/date: FDA, 2024-05-15
Product: Lisocabtagene maraleucel (Breyanzi; Juno Therapeutics, Inc.)
Indication: Adults with relapsed or refractory follicular lymphoma who have received two or more prior lines of systemic therapy.

Supporting evidence

Efficacy was evaluated in TRANSCEND-FL (NCT04245839), a phase 2, open-label, multicenter, single-arm trial in adults with R/R FL after ≥2 prior lines (including an anti-CD20 antibody and an alkylating agent). Patients had ECOG performance status ≤1 and adequate marrow function for lymphodepleting chemotherapy. Bridging therapy for disease control was permitted.

Patients received lymphodepletion with fludarabine 30 mg/m²/day and cyclophosphamide 300 mg/m²/day concurrently for 3 days, followed by a single liso-cel infusion 2–7 days later.

The primary efficacy population included 94 patients with PET-positive disease at baseline or after bridging therapy, who received conforming product in the intended dose range and had ≥9 months follow-up from first response.

Outcomes (independent review):

  • ORR: 95.7% (95% CI, 89.5–98.8)
  • Median DOR: not reached (95% CI, 18.04–NR) at median follow-up 16.8 months

Safety/requirements

Common nonlaboratory adverse reactions (≥20%) included CRS, headache, musculoskeletal pain, fatigue, constipation, and fever. FDA approved liso-cel with a REMS due to risk of fatal or life-threatening CRS and neurologic toxicities.

Recommended dose: 90–110 × 10^6 CAR-positive viable T cells with a 1:1 CD4:CD8 ratio.

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