Michael Wang; Javier Muñoz; André Goy; Frederick L. Locke; Caron A. Jacobson; Brian T. Hill; John M. Timmerman; Houston Holmes; Samantha Jaglowski; Ian W. Flinn; Peter A. McSweeney; David B. Miklos; John M. Pagel; Marie José Kersten; Nöel Milpied; Henry C. Fung; Max S. Topp; Roch Houot; Amer Beitinjaneh; Weimin Peng; Lianqing Zheng; John M. Rossi; Rajul K. Jain; Arati V. Rao; Patrick M. Reagan · 2020 · New England Journal of Medicine
Paper
BACKGROUND: Patients with relapsed or refractory mantle-cell lymphoma who have disease progression during or after the receipt of Bruton's tyrosine kinase (BTK) inhibitor therapy have a poor prognosis. KTE-X19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, may have benefit in patients with relapsed or refractory mantle-cell lymphoma. METHODS: CAR T cells per kilogram of body weight. The primary end point was the percentage of patients with an objective response (complete or partial response) as assessed by an independent radiologic review committee according to the Lugano classification. Per the protocol, the primary efficacy analysis was to be conducted after 60 patients had been treated and followed for 7 months. RESULTS: A total of 74 patients were enrolled. KTE-X19 was manufactured for 71 patients and administered to 68. The primary efficacy analysis showed that 93% (95% confidence interval [CI], 84 to 98) of the 60 patients in the primary efficacy analysis had an objective response; 67% (95% CI, 53 to 78) had a complete response. In an intention-to-treat analysis involving all 74 patients, 85% had an objective response; 59% had a complete response. At a median follow-up of 12.3 months (range, 7.0 to 32.3), 57% of the 60 patients in the primary efficacy analysis were in remission. At 12 months, the estimated progression-free survival and overall survival were 61% and 83%, respectively. Common adverse events of grade 3 or higher were cytopenias (in 94% of the patients) and infections (in 32%). Grade 3 or higher cytokine release syndrome and neurologic events occurred in 15% and 31% of patients, respectively; none were fatal. Two grade 5 infectious adverse events occurred. CONCLUSIONS: KTE-X19 induced durable remissions in a majority of patients with relapsed or refractory mantle-cell lymphoma. The therapy led to serious and life-threatening toxic effects that were consistent with those reported with other CAR T-cell therapies. (Funded by Kite, a Gilead company; ZUMA-2 ClinicalTrials.gov number, NCT02601313.).
Analysis
This study evaluates the efficacy and safety of KTE-X19, an anti-CD19 CAR T-cell therapy, in patients with relapsed or refractory mantle-cell lymphoma.
Discovery
Estelle Baulu; Célia Gardet; Nicolas Chuvin; Stéphane Depil
Silvia Arcangeli; Camilla Bove; Claudia Mezzanotte; Barbara Camisa; Laura Falcone; Francesco Manfredi; Eugenia Bezzecchi; Rita El Khoury; Rossana Norata; Francesca Sanvito; Maurilio Ponzoni; Beatrice Greco; Marta Angiola Moresco; Matteo G. Carrabba; Fabio Ciceri; Chiara Bonini; Attilio Bondanza; Monica Casucci
Robert C. Sterner; Rosalie M. Sterner; Rosalie M. Sterner; Rosalie M. Sterner
Matteo Morotti; Ashwag Albukhari; Abdulkhaliq Alsaadi; Mara Artibani; James D. Brenton; Stuart M. Curbishley; Tao Dong; Michael L. Dustin; Zhiyuan Hu; Nicholas McGranahan; Martin L. Miller; Laura Santana-Gonzalez; Leonard W. Seymour; Tingyan Shi; Peter Van Loo; Christopher Yau; Helen White; Nina Wietek; David N. Church; David C. Wedge; Ahmed A. Ahmed
Yongxian Hu; Yali Zhou; Mingming Zhang; Wengang Ge; Yi Li; Li Yang; Guoqing Wei; Lu Han; Hao Wang; Shuhui Yu; Yi Chen; Yanbin Wang; Xiaohong He; Xingwang Zhang; Ming Gao; Jingjing Yang; Xiuju Li; Jiangtao Ren; He Huang
Joe-Marc Chauvin; Hassane M Zarour
Source record