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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Clinical Efficacy and Tumor Microenvironment Influence in a Dose-Escalation Study of Anti-CD19 Chimeric Antigen Receptor T Cells in Refractory B-Cell Non-Hodgkin's Lymphoma
Zi Xun Yan,Li Li,Wen Wang,Bin Shen OuYang,Shu Cheng,Li Wang,Wen Wu,P P Xu,Muharrem Muftuoglu,Ming Hao,Su Yang,Mu Chen Zhang,Zhong Zheng,James Li,Wei Li Zhao +14 more
TL;DR: The composition of the tumor microenvironment has a potential impact in CAR T therapy response and was effective and safe in treating refractory B-NHL.
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CRISPR/Cas9 and CAR-T cell, collaboration of two revolutionary technologies in cancer immunotherapy, an instruction for successful cancer treatment.
TL;DR: The combination of CRISPR/Cas9 technology as a genome engineering tool and CAR-T cell therapy (engineered T cells that express chimeric antigen receptors) may lead to further improvement in efficiency and safety ofCAR-T cells.
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Value and affordability of CAR T-cell therapy in the United States
Salvatore Fiorenza,David Ritchie,David Ritchie,Scott D. Ramsey,Scott D. Ramsey,Cameron J. Turtle,Cameron J. Turtle,Joshua A. Roth,Joshua A. Roth +8 more
TL;DR: Recent, peer-reviewed cost-effectiveness studies of tisagenlecleucel and axicabtagene ciloleucel in the United States are summarized; key issues concerning the health plan budget impact of CAR T-cell therapy are discussed; and policy, payment and scientific approaches that may improve the value and affordability are reviewed.
Journal ArticleDOI
Management of cytokine release syndrome and neurotoxicity in chimeric antigen receptor (CAR) T cell therapy
Utkarsh Acharya,Tejaswini Dhawale,Seongseok Yun,Caron A. Jacobson,Julio C. Chavez,Jorge Ramos,Jacob S. Appelbaum,David G. Maloney +7 more
TL;DR: This manuscript provides an in-depth overview of the pathogenesis, clinical characteristics, current toxicity management strategies, and future perspectives pertaining to CRS and neurotoxicity.
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Long-term safety and activity of NY-ESO-1 SPEAR T cells after autologous stem cell transplant for myeloma.
Edward A. Stadtmauer,Thomas H. Faitg,Daniel E. Lowther,Ashraf Badros,Karen Chagin,Karen Dengel,Malini Iyengar,Luca Melchiori,Jean-Marc Navenot,Elliot Norry,Trupti Trivedi,Ruoxi Wang,Gwendolyn K. Binder,Rafael G. Amado,Aaron P. Rapoport +14 more
TL;DR: In this MM patient population, NY-ESO-1 SPEAR T-cell therapy in the context of ASCT was associated with antitumor activity and was well tolerated; cytokine release syndrome was not reported.
References
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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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