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
Citations
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Current Challenges in Providing Good Leukapheresis Products for Manufacturing of CAR-T Cells for Patients with Relapsed/Refractory NHL or ALL.
Felix Korell,Sascha Laier,Sandra Sauer,Kaya Veelken,Hannah Mai Hennemann,Maria-Luisa Schubert,Tim Sauer,Petra Pavel,Carsten Mueller-Tidow,Peter Dreger,Michael Schmitt,Anita Schmitt +11 more
TL;DR: Sufficient yield of lymphocytes for CAR-T cell production is feasible also for patients with low peripheral blood counts, and up to 12–15 L blood volume should be processed in patients with absolute lymphocyte counts ≤ 1.0/nL.
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Modified EASIX predicts severe cytokine release syndrome and neurotoxicity after chimeric antigen receptor T cells
Martina Pennisi,Martina Pennisi,Miriam Sanchez-Escamilla,Jessica Flynn,Roni Shouval,Ana Alarcon Tomas,Mari Lynne Silverberg,Connie Lee Batlevi,Renier J. Brentjens,Parstoo B Dahi,Parstoo B Dahi,Sean M. Devlin,Claudia Diamonte,Sergio Giralt,Sergio Giralt,Elizabeth Halton,Tania Jain,Molly Maloy,Elena Mead,Maria Lia Palomba,Josel D. Ruiz,Bianca Santomasso,Craig S. Sauter,Craig S. Sauter,Michael Scordo,Michael Scordo,Gunjan L. Shah,Gunjan L. Shah,Jae H. Park,Lucrecia Yanez San Segundo,Miguel-Angel Perales,Miguel-Angel Perales +31 more
TL;DR: In this paper, the EASIX score (lactate dehydrogenase [LDH; U/L] × creatinine [mg/dL]/platelets [PLTs; 109 cells/L]) is a marker of endothelial damage that correlates with outcomes in allogeneic hematopoietic cell transplantation.
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Immunotherapy Deriving from CAR-T Cell Treatment in Autoimmune Diseases.
TL;DR: Using the idea of CAR-T cell treatment in tumors, CAR- T cell-derived immunotherapies, chimeric autoantibody receptor T (CAAR-T), and CAR regulatory T (CAR-T) cells bring new hope of treatment choice for AIDs.
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The Chimeric Antigen Receptor Detection Toolkit.
TL;DR: A review of the plethora of CAR detection methods, which can operate at the genomic, transcriptomic, proteomic, and organismal levels, and considers current scientific and clinical needs in order to provide future perspectives for improved CAR detection.
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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