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
CAR T-Cell Therapy in Hematologic Malignancies: A Voyage in Progress.
TL;DR: An overview of the rapidly evolving landscape of CAR T‐cell therapy in hematological malignancies is provided and the advances that will shape the future of this field are looked at.
Journal ArticleDOI
Homozygous BCMA gene deletion in response to anti-BCMA CAR T cells in a patient with multiple myeloma
Matteo C. Da Vià,Oliver Dietrich,Marietta Truger,Panagiota Arampatzi,Johannes Duell,Anke Heidemeier,Xiang Zhou,Sophia Danhof,Sabrina Kraus,Manik Chatterjee,Manja Meggendorfer,Sven Twardziok,Maria-Elisabeth Goebeler,Max S. Topp,Michael Hudecek,Sabrina Prommersberger,Kristen Hege,Shari Kaiser,Viktoria Fuhr,Niels Weinhold,Andreas Rosenwald,Florian Erhard,Claudia Haferlach,Hermann Einsele,K. Martin Kortüm,Antoine-Emmanuel Saliba,Leo Rasche +26 more
TL;DR: In this paper, the authors reported a case of irreversible BCMA loss in a patient with multiple myeloma who was enrolled in the KarMMa trial and progressed after anti-BCMA CAR T cell therapy and identified selection of a clone with homozygous deletion of TNFRSF17 as the underlying mechanism of immune escape.
Journal ArticleDOI
Toxicities of CD19 CAR-T cell immunotherapy.
TL;DR: CD19‐targeted chimeric antigen receptor (CAR)‐modified T (CAR‐T) cell immunotherapy has demonstrated impressive results in B‐cell malignancies, and CAR‐T cell therapies targeting other antigens are in development for other cancers.
Journal ArticleDOI
CAR T cell killing requires the IFNγR pathway in solid but not liquid tumours
Rebecca C. Larson,Michael Kann,Stefanie R. Bailey,Nicholas J. Haradhvala,Paula Montero Llopis,Amanda A. Bouffard,Irene Scarfò,Mark B. Leick,Korneel Grauwet,Trisha R. Berger,Kai Stewart,Praju Anekal,Max Jan,J. Keith Joung,Andrea Schmidts,Tamara Ouspenskaia,Travis Law,Aviv Regev,Gad Getz,Marcela V. Maus +19 more
TL;DR: It is found that liquid and solid tumours differ in their interactions with CAR T cells and this work suggests that enhancing binding interactions between T cell and tumour cells may yield improved responses inSolid tumours.
Journal ArticleDOI
Preclinical Evaluation of Allogeneic CAR T Cells Targeting BCMA for the Treatment of Multiple Myeloma.
Cesar Sommer,Bijan Boldajipour,Tracy C. Kuo,Trevor Bentley,Janette Sutton,Chen Amy Shaw-Ru,Tao Geng,Holly Dong,Roman Galetto,Julien Valton,Thomas Pertel,Alexandre Juillerat,Annabelle Gariboldi,Pascua Edward Derrick,Colleen Brown,Sherman M. Chin,Tao Sai,Yajin Ni,Philippe Duchateau,Julianne Smith,Arvind Rajpal,Thomas Van Blarcom,Javier Chaparro-Riggers,Barbra Sasu +23 more
TL;DR: This novel off-the-shelf allogeneic BCMA CAR T product is a promising candidate for clinical evaluation and induced sustained antitumor responses in mice supplemented with human cytokines, and maintained their phenotype and potency after scale-up manufacturing.
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