June 2022: After two or more lines of systemic therapy, the FDA awarded tisagenlecleucel (Kymriah, Novartis Pharmaceuticals Corporation) expedited approval for adult patients with relapsed or refractory follicular lymphoma (FL).
The approval was based on the results of the ELARA trial (NCT03568461), a multicenter, single-arm, open-label trial evaluating tisagenlecleucel, a CD19-directed chimeric antigen receptor (CAR) T cell therapy, in adult patients who were refractory or relapsed within 6 months after completing two or more lines of systemic therapy (including an anti-CD20 antibody and an alkylating agent) or Tisagenlecleucel was given as a single intravenous infusion after lymphodepleting chemotherapy, with a target dosage of 0.6 to 6.0 x 108 CAR-positive viable T cells.
The overall response rate (ORR) and duration of response (DOR), as established by an independent review committee, were the major efficacy measures. The ORR was 86 percent (95 percent CI: 77, 92) among 90 patients in the primary efficacy analysis, with a CR rate of 68 percent (95 percent CI: 57, 77). The median DOR was not met, with 75% of respondents (95 percent CI: 63, 84) still responding after 9 months. The ORR was 86 percent (95 percent CI: 77, 92) for all patients who had leukapheresis (n=98), with a CR rate of 67 percent (95 percent CI: 57, 76).
Cytokine release syndrome, infection, weariness, musculoskeletal pain, headache, and diarrhoea were the most prevalent adverse effects in patients (>20 percent). 0.6 to 6.0 x 108 CAR-positive viable T cells is the suggested tisagenlecleucel dose.