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
More filters
Journal ArticleDOI
Mitigating the risk of cytokine release syndrome in a Phase I trial of CD20/CD3 bispecific antibody mosunetuzumab in NHL: impact of translational system modeling
Iraj Hosseini,Kapil Gadkar,Eric Stefanich,Chi-Chung Li,Liping L. Sun,Yu-Waye Chu,Saroja Ramanujan +6 more
TL;DR: A novel mechanistic model of immune and antitumor responses to the T-cell bispecifics, including the dynamics of B- and T-lymphocytes in circulation, lymphoid tissues, and tumor, supported a change to a step-fractionated treatment schedule of mosunetuzumab in the ongoing Phase I clinical trial, enabling safer administration of higher doses.
Journal ArticleDOI
Understanding and Managing Large B Cell Lymphoma Relapses after Chimeric Antigen Receptor T Cell Therapy
Michael Byrne,Olalekan O. Oluwole,Bipin N. Savani,Navneet S. Majhail,Brian T. Hill,Fredrick L. Locke +5 more
TL;DR: This manuscript reviews possible mechanisms of treatment failures and, based on the timing of relapse, considers potential salvage therapies and opportunities for future clinical studies.
Journal ArticleDOI
Allogeneic FLT3 CAR T Cells with an Off-Switch Exhibit Potent Activity against AML and Can Be Depleted to Expedite Bone Marrow Recovery.
Cesar Sommer,Hsin-Yuan Cheng,Duy Nguyen,Danielle Dettling,Yik Andy Yeung,Janette Sutton,Moustafa Hamze,Julien Valton,Julianne Smith,Ivana Djuretic,Javier Chaparro-Riggers,Barbra Sasu +11 more
TL;DR: It is found that allogeneic FLT3 CAR T-cells, generated from healthy-donor T cells, eliminate primary AML blasts but are also active against mouse and human hematopoietic stem and progenitor cells, indicating risk of myelotoxicity.
Journal ArticleDOI
Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma.
Michael Dickinson,Carmelo Carlo-Stella,Franck Morschhauser,Emmanuel Bachy,Paolo Corradini,Gloria Iacoboni,Cyrus Khan,Tomasz Wróbel,Fritz Offner,Marek Trneny,Shang-Ju Wu,Guillaume Cartron,Mark P. Hertzberg,Anna Sureda,David Pérez-Callejo,Linda Lundberg,James Relf,Mark Dixon,Emma Clark,Kathryn Humphrey,Martin Hutchings +20 more
TL;DR: In the phase 2 part of a phase 1-2 study, this paper enrolled 155 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who had received at least two lines of therapy previously.
Journal ArticleDOI
Enhanced safety and efficacy of protease-regulated CAR-T cell receptors
Louai Labanieh,Robbie G. Majzner,Dorota Klysz,Elena Sotillo,Christopher J. Fisher,Jose G. Vilches-Moure,K. Z. Pacheco,Meena Malipatlolla,Peng Xu,Jessica Hui,Tara Murty,Johanna Theruvath,Nishant Mehta,Sean A. Yamada-Hunter,Evan W. Weber,Sabine Heitzeneder,Kevin R. Parker,Ansuman T. Satpathy,Howard Y. Chang,Michael Z. Lin,Jennifer R. Cochran,Crystal L. Mackall +21 more
TL;DR: SNIP CARs as discussed by the authors is a protease-based platform for regulating CAR activity using an FDA-approved small molecule, and it has been shown that drug cessation following toxicity onset reversed toxicity, thereby credentialing the platform as a safety switch.
References
More filters
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.
Related Papers (5)
Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia
Shannon L. Maude,Theodore W. Laetsch,Jochen Buechner,S. Rives,Michael Boyer,Henrique Bittencourt,Peter Bader,Michael R. Verneris,Heather E. Stefanski,G.D. Myers,Muna Qayed,B. De Moerloose,Hidefumi Hiramatsu,Krysta Schlis,Kara L. Davis,Paul L. Martin,Eneida R. Nemecek,Gregory A. Yanik,Christina Peters,André Baruchel,Nicolas Boissel,Francoise Mechinaud,Adriana Balduzzi,Joerg Krueger,Carl H. June,Bruce L. Levine,Patricia A. Wood,Tanya Taran,Mimi Leung,Karen Thudium Mueller,Yiyun Zhang,Kapildeb Sen,David Lebwohl,Michael A. Pulsipher,Stephan A. Grupp +34 more
Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Stephen J. Schuster,Michael R. Bishop,Constantine S. Tam,Edmund K. Waller,Peter Borchmann,Joseph P. McGuirk,Ulrich Jäger,Samantha Jaglowski,Charalambos Andreadis,Jason R. Westin,Isabelle Fleury,Veronika Bachanova,S. Ronan Foley,P. Joy Ho,Stephan Mielke,Stephan Mielke,John M. Magenau,Harald Holte,Serafino Pantano,Lida Bubuteishvili Pacaud,Rakesh Awasthi,Jufen Chu,Özlem Anak,Gilles Salles,Richard T. Maziarz +24 more
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