Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia
Maude, S (Contributor), Laetsch, T (Contributor), Buechner, J (Contributor), Rives, S (Contributor), Boyer, M (Contributor), Bittencourt, H (Contributor), Bader, P (Contributor), Verneris, M (Contributor), Stefanski, H (Contributor), Myers, G (Contributor), Qayed, M (Contributor), De Moerloose, B (Contributor), Hiramatsu, H (Contributor), Schlis, K (Contributor), Davis, K (Contributor), Martin, P (Contributor), Nemecek, E (Contributor), Yanik, G (Contributor), Peters, C (Contributor), Baruchel, A (Contributor), Boissel, N (Contributor), Mechinaud, F (Contributor), Balduzzi, A (Contributor), Krueger, J (Contributor), June, C (Contributor), Levine, B (Contributor), Wood, P (Contributor), Taran, T (Contributor), Leung, M (Contributor), Mueller, K (Contributor), Zhang, Y (Contributor), Sen, K (Contributor), Lebwohl, D (Contributor), Pulsipher, M (Contributor), Grupp, S (Contributor), Maude SL (Creator), Laetsch TW (Creator), Buechner J (Creator), Rives S (Creator), Boyer M (Creator), Bittencourt H (Creator), Bader P (Creator), Verneris MR (Creator), Stefanski HE (Creator), Myers GD (Creator), Qayed M (Creator), De Moerloose B (Creator), Hiramatsu H (Creator), Schlis K (Creator), Davis KL (Creator)
BACKGROUND In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). METHODS We conducted a phase 2, single-cohort, 25-center, global study of tisagenlecleucel in pediatric and young adult patients with CD19+ relapsed or refractory B-cell ALL. The primary end point was the overall remission rate (the rate of complete remission or complete remission with incomplete hematologic recovery) within 3 months. RESULTS For this planned analysis, 75 patients received an infusion of tisagenlecleucel and could be evaluated for efficacy. The overall remission rate within 3 months was 81%, with all patients who had a response to treatment found to be negative for minimal residual disease, as assessed by means of flow cytometry. The rates of event-free survival and overall survival were 73% (95% confidence interval [CI], 60 to 82) and 90% (95% CI, 81 to 95), respectively, at 6 months and 50% (95% CI, 35 to 64) and 76% (95% CI, 63 to 86) at 12 months. The median duration of remission was not reached. Persistence of tisagenlecleucel in the blood was observed for as long as 20 months. Grade 3 or 4 adverse events that were suspected to be related to tisagenlecleucel occurred in 73% of patients. The cytokine release syndrome occurred in 77% of patients, 48% of whom received tocilizumab. Neurologic events occurred in 40% of patients and were managed with supportive care, and no cerebral edema was reported. CONCLUSIONS In this global study of CAR T-cell therapy, a single infusion of tisagenlecleucel provided durable remission with long-term persistence in pediatric and young adult patients with relapsed or refractory B-cell ALL, with transient high-grade toxic effects
Downloadable Archival Material, English, 2018