Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma
Sattva S. Neelapu,Frederick L. Locke,Nancy L. Bartlett,Lazaros J. Lekakis,David B. Miklos,Caron A. Jacobson,Ira Braunschweig,Olalekan O. Oluwole,Tanya Siddiqi,Yi Lin,John M. Timmerman,Patrick J. Stiff,Jonathan W. Friedberg,Ian W. Flinn,Andre Goy,Brian T. Hill,Mitchell R. Smith,Abhinav Deol,Umar Farooq,Peter A. McSweeney,Javier Munoz,Irit Avivi,Januario E. Castro,Jason R. Westin,Julio C. Chavez,Armin Ghobadi,Krishna V. Komanduri,Ronald Levy,Eric D. Jacobsen,Thomas E. Witzig,Patrick M. Reagan,Adrian Bot,John J. Rossi,Lynn Navale,Yizhou Jiang,Jeff Aycock,Meg Elias,David Z. Chang,Jeff Wiezorek,William Y. Go +39 more
TLDR
Patients with refractory large B‐cell lymphoma who received CAR T‐cell therapy with axi‐cel had high levels of durable response, with a safety profile that included myelosuppression, the cytokine release syndrome, and neurologic events.Abstract:
BackgroundIn a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy. MethodsIn this multicenter, phase 2 trial, we enrolled 111 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy. Patients received a target dose of 2×106 anti-CD19 CAR T cells per kilogram of body weight after receiving a conditioning regimen of low-dose cyclophosphamide and fludarabine. The primary end point was the rate of objective response (calculated as the combined rates of complete response and partial response). Secondary end points included overall survival, safety, and biomarker assessments. ResultsAmong the 111 patients who were enrolled, axi-cel was successfully manufactured for 110 (99%) and administered to 101 (91%)....read more
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References
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Thierry Philip,Cesare Guglielmi,Anton Hagenbeek,Riet Somers,H. Van der Lelie,Dominique Bron,Pieter Sonneveld,Christian Gisselbrecht,Jean-Yves Cahn,Jean Luc Harousseau +9 more
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Efficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B Cell Acute Lymphoblastic Leukemia
Marco L. Davila,Isabelle Riviere,Xiuyan Wang,Shirley Bartido,Jae H. Park,Kevin J. Curran,Stephen S. Chung,Jolanta Stefanski,Oriana Borquez-Ojeda,Malgorzata Olszewska,Jinrong Qu,Teresa Wasielewska,Qing He,Mitsu Fink,Himaly Shinglot,Maher Youssif,Mark Satter,Yongzeng Wang,James Hosey,Hilda Quintanilla,Elizabeth Halton,Yvette Bernal,Diana C. G. Bouhassira,Maria E. Arcila,Mithat Gonen,Gail J. Roboz,Peter Maslak,Dan Douer,Mark G. Frattini,Sergio Giralt,Michel Sadelain,Renier J. Brentjens +31 more
TL;DR: Diagnostic criteria for a severe cytokine release syndrome (sCRS) is defined and serum C-reactive protein, a readily available laboratory study, can serve as a reliable indicator for the severity of the CRS.
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