On May 27, 2022, the U.S. Food and Drug Administration (FDA) granted accelerated approval to tisagenlecleucel (Kymriah®) for adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy.
The approval was based on a multicenter, single-arm, open-label trial (ELARA; NCT03568461) evaluating tisagenlecleucel, a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, in adult patients who were refractory or relapsed within six months after completion of two or more lines of systemic therapy, including an anti-CD20 antibody and an alkylating agent, or relapsed after autologous hematopoietic stem cell transplant. Following lymphodepleting chemotherapy, tisagenlecleucel was administered as a single IV infusion with a target dose of 0.6–6.0 x 108 CAR-positive viable T cells.
The main efficacy measures were overall response rate (ORR) and duration of response (DOR) as determined by an independent review committee. Among 90 patients in the primary efficacy analysis, the ORR was 86% (95% CI = 77, 92) with a complete response (CR) rate of 68% (95% CI = 57, 77). The median DOR was not reached, with 75% (95% CI = 63, 84) of responders still in response at nine months. For all patients who underwent leukapheresis (n = 98), ORR was 86% (95% CI = 77, 92) with a CR rate of 67% (95% CI = 57, 76).
The most common adverse reactions reported in more than 20% of patients were cytokine release syndrome, infection, fatigue, musculoskeletal pain, headache, and diarrhea.
The recommended tisagenlecleucel dose is 0.6–6.0 x 108 CAR-positive viable T cells.
View the full prescribing information for tisagenlecleucel.
The indication received accelerated approval based on response rate. Continued approval for the indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
The review used the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. FDA approved the application one month ahead of FDA’s goal date. The application was granted priority review and regenerative medicine advanced therapy designation. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics. The application also was granted orphan drug designation.
Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.
For assistance with single-patient investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.