On May 27, 2022, tisagenlecleucel, a CD19 chimeric antigen receptor (CAR) T-cell therapy, was granted accelerated approval for adults with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.1
Supporting Efficacy Data
Approval was based on the multicenter ELARA trial (ClinicalTrials.gov identifier NCT03568461) in patients who were refractory or relapsed within 6 months after completion of at least two lines of systemic therapy (including an anti-CD20 antibody and an alkylating agent) or who relapsed after autologous hematopoietic stem cell transplantation. Following lymphodepleting chemotherapy, tisagenlecleucel was given via a single intravenous infusion with a target dose of 0.6 to 6.0 × 108 chimeric antigen receptor (CAR)-positive viable T cells.
In the primary efficacy population of 90 patients, a response (complete or partial) was achieved in 77 (86%, 95% confidence interval [CI] = 77%–92%), with a complete response in 61 (68%, 95% CI = 57%–77%). The median duration of response was not reached, with 75% of responders still in response at 9 months. Among patients with a complete response, 88% of responders remained in response at 9 months. Among 98 patients who underwent leukapheresis, the overall response rate was 86% (95% CI = 77%–92%).
How It Is Used
Tisagenlecleucel is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Kymriah REMS. The recommended tisagenlecleucel dose is 0.6 to 6.0 × 108 CAR-positive viable T cells. Product labeling provides instructions on lymphodepleting treatment, premedication, and management of adverse reactions including cytokine-release syndrome and neurologic toxicity including immune effector cell–associated neurotoxicity syndrome.
Among the 97 patients in the ELARA trial who received tisagenlecleucel, the most common adverse events of any grade were cytokine-release syndrome (53%, all grade 1 or 2), infection (38%), fatigue (27%), musculoskeletal pain (25%), headache (25%), and diarrhea (24%).
Tisagenlecleucel has boxed warnings for cytokine-release syndrome and neurologic toxicities. It also carries warnings/precautions for hypersensitivity reactions, serious infections, prolonged cytopenias, hypogammaglobulinemia, secondary malignancies, and effects on the ability to drive and use machines.
1. Kymriah (tisagenlecleucel) suspension for intravenous infusion prescribing information, Novartis, May 2022. Available at www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/kymriah-tisagenlecleucel. Accessed June 6, 2022.