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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Factors associated with outcomes after a second CD19-targeted CAR T-cell infusion for refractory B-cell malignancies
Jordan Gauthier,Evandro D. Bezerra,Alexandre V. Hirayama,Salvatore Fiorenza,Alyssa Sheih,Cassie K. Chou,Erik Kimble,Barbara S. Pender,Reed M. Hawkins,Aesha Vakil,Tinh-Doan Phi,Rachel N. Steinmetz,Abby W. Jamieson,Merav Bar,Ryan D. Cassaday,Aude G. Chapuis,Andrew J. Cowan,Damian J. Green,Hans-Peter Kiem,Filippo Milano,Mazyar Shadman,Brian G. Till,Stanley R. Riddell,David G. Maloney,Cameron J. Turtle +24 more
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References
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Book
WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues
TL;DR: Thank you very much for reading who classification of tumours of haematopoietic and lymphoid tissues, and maybe you have knowledge that, people have look hundreds of times for their chosen readings like this, but end up in malicious downloads.
Journal ArticleDOI
Chimeric antigen receptor T cells for sustained remissions in leukemia.
Shannon L. Maude,Noelle Frey,Pamela A. Shaw,Richard Aplenc,David M. Barrett,Nancy Bunin,Anne Chew,Vanessa E. Gonzalez,Zhaohui Zheng,Simon F. Lacey,Yolanda D. Mahnke,J. Joseph Melenhorst,Susan R. Rheingold,Angela Shen,David T. Teachey,Bruce L. Levine,Carl H. June,David L. Porter,Stephan A. Grupp +18 more
TL;DR: Chimeric antigen receptor-modified T-cell therapy against CD19 was effective in treating relapsed and refractory ALL and was associated with a high remission rate, even among patients for whom stem-cell transplantation had failed, and durable remissions up to 24 months were observed.
Journal ArticleDOI
Revised response criteria for malignant lymphoma
Bruce D. Cheson,Beate Pfistner,Malik E. Juweid,Randy D. Gascoyne,Lena Specht,Sandra J. Horning,Bertrand Coiffier,Richard I. Fisher,Anton Hagenbeek,Emanuele Zucca,Steven T. Rosen,Sigrid Stroobants,T. Andrew Lister,Richard T. Hoppe,Martin Dreyling,Kensei Tobinai,Julie M. Vose,Joseph M. Connors,Massimo Federico,Volker Diehl +19 more
TL;DR: New guidelines incorporating PET, IHC, and flow cytometry for definitions of response in non-Hodgkin's and Hodgkin's lymphoma are presented and it is hoped that they will be adopted widely by study groups, pharmaceutical and biotechnology companies, and regulatory agencies to facilitate the development of new and more effective therapies to improve the outcome of patients with lymphoma.
Journal ArticleDOI
Autologous Bone Marrow Transplantation as Compared with Salvage Chemotherapy in Relapses of Chemotherapy-Sensitive Non-Hodgkin's Lymphoma
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
TL;DR: Treatment with high-dose chemotherapy and autologous bone marrow transplantation increases event-free and overall survival in patients with chemotherapy-sensitive non-Hodgkin's lymphoma in relapse.
Journal ArticleDOI
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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