The U.S. Food and Drug Administration's Oncologic Drugs Advisory Committee (ODAC) voted 10-0 in favor of recommending approval for tisagenlecleucel (formerly known as CTL019), an investigational chimeric antigen receptor (CAR) T-cell therapy, for treatment of pediatric and young adult patients with relapsed/refractory B-cell acute lymphocytic leukemia (ALL). If approved, tisagenlecleucel would be the first CAR T-cell therapy on the market.
ODAC's decision was primarily based on data from the phase II ELIANA trial and two other supporting trials encompassing 97 pediatric and young adult patients with relapsed/refractory B-cell ALL who were treated with tisagenlecleucel. At three-month follow-up, the overall response rate (ORR; including complete remission or complete remission with incomplete platelet recovery) ranged from 69.0 percent to 94.5 percent across the three trials.
Reviewers determined that the results from the three trials offered "compelling evidence" about the drug's efficacy and the safety profile was "well-characterized" with manageable toxicity. As with other CAR T-cell therapies, cytokine release syndrome (CRS) was the adverse event (AE) of most concern; 48 percent (n=32) of patients in the ELIANA trial developed grade 3/4 CRS. Fifteen percent of patients experienced grade 3 neurologic and psychiatric AEs (including confusion, delirium, encephalopathy, agitation, and seizure), but no cerebral edema was reported.
Sources: Novartis press release, July 12, 2017 and March 29, 2017; FDA ODAC Briefing Document, July 12, 2017.