Article
作者: de Vos, Sven ; Berent-Maoz, Beata ; Ceja, Melanie Ayala ; Naparstek, Jacob ; Schiller, Gary J. ; Timmerman, John M. ; Chen, Yvonne Y. ; Larson, Sarah M. ; Roshandell, Mobina ; Nawaly, Karla ; Harris, Caitlin ; Gosliner, Stanley B. ; Allen-Auerbach, Martin S. ; Young, Patricia A. ; Ji, Brenda ; Mead, Monica ; Schweppe, Thomas ; Khericha, Mobina ; Walthers, Christopher M. ; Almaktari, Amr ; Ribas, Antoni ; Said, Jonathan ; Chen, Jia Ming ; Oliai, Caspian ; Ghafouri, Sanaz N. ; Trent, Jacqueline
Abstract:To address antigen escape and loss of T-cell functionality, we report a phase I clinical trial (NCT04007029) evaluating autologous naive and memory T (TN/MEM) cells engineered to express a bispecific anti-CD19/CD20 chimeric antigen receptor (CAR; CART19/20) for patients with relapsed/refractory non-Hodgkin lymphoma (NHL), with safety as the primary endpoint. Ten patients were treated with 36 × 106 to 165 × 106 CART19/20 cells. No patient experienced neurotoxicity of any grade or over grade 1 cytokine release syndrome. One case of dose-limiting toxicity (persistent cytopenia) was observed. Nine of 10 patients achieved objective response [90% overall response rate (ORR)], with seven achieving complete remission [70% complete responses (CR) rate]. One patient relapsed after 18 months in CR but returned to CR after receiving a second dose of CART19/20 cells. Median progression-free survival was 18 months and median overall survival was not reached with a 17-month median follow-up. In conclusion, CART19/20 TN/MEM cells are safe and effective in patients with relapsed/refractory NHL, with durable responses achieved at low dosage levels.
Significance::Autologous CD19/CD20 bispecific CAR-T cell therapy generated from TN/MEM cells for patients with NHL is safe (no neurotoxicity, maximum grade 1 cytokine release syndrome) and demonstrates strong efficacy (90% ORR, 70% CR rate) in a first-in-human, phase I dose-escalation trial.This article is highlighted in the In This Issue feature, p. 517