On May 27, 2022, the FDA accelerated the approval of a new indication for the CD19-directed CAR T-cell therapy tisagenlecleucel (Kymriah; Novartis) for adults with relapsed or refractory follicular lymphoma after ≥2 lines of systemic therapy. The FDA granted this indication an orphan drug designation.
“The approval of Kymriah offers patients with relapsed or refractory follicular lymphoma a new treatment option and new hope for improving patient outcomes,” Meghan Gutierrez, Chief Executive Officer, Lymphoma Research Foundation, said in a press release. “Having this single infusion treatment option helps to transform the way healthcare providers approach this type of blood cancer.”
The approval was based on the ELARA study, a multicenter, single-arm, open-label clinical trial of adults with relapsed or refractory follicular lymphoma within 6 months after completion of ≥2 lines of systemic therapy (including an anti-CD20 antibody and an alkylating agent) or relapsed after autologous hematopoietic stem-cell transplant.
The main efficacy measures were overall response rate (ORR) and duration of response (DOR). Among the 90 patients in the primary efficacy analysis, the ORR was 86% (95% confidence interval [CI], 77-92), including 68% complete responses. At 9 months, the median DOR was not reached, and 75% of those with a response were still responding to the CAR T-cell therapy. For the 98 patients who underwent leukapheresis, the ORR was 86% (95% CI, 77-92), including 67% complete responses.
The most common (>20%) adverse reactions were cytokine-release syndrome, infection, fatigue, musculoskeletal pain, headache, and diarrhea.
Continued approval for this indication may be contingent on verification of the clinical benefit in confirmatory trial(s).