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
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TLDR
In this global study of CAR T‐cell therapy, a single infusion of tisagenlecleucel provided durable remission with long‐term persistence in pediatric and young adult patients with relapsed or refractory B‐cell ALL, with transient high‐grade toxic effects.Abstract:
Background In a single-center phase 1–2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) Methods We conducted a phase 2, single-cohort, 25-center, global study of tisagenlecleucel in pediatric and young adult patients with CD19+ relapsed or refractory B-cell ALL The primary end point was the overall remission rate (the rate of complete remission or complete remission with incomplete hematologic recovery) within 3 months Results For this planned analysis, 75 patients received an infusion of tisagenlecleucel and could be evaluated for efficacy The overall remission rate within 3 months was 81%, with all patients who had a response to treatment found to be negative for minimal residual disease, as assessed by means of flow cytometry The rates of event-fread more
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Journal ArticleDOI
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
TL;DR: The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study.
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CAR T cell immunotherapy for human cancer
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ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells
Daniel W. Lee,Bianca Santomasso,Frederick L. Locke,Armin Ghobadi,Cameron J. Turtle,Jennifer N. Brudno,Marcela V. Maus,Jae H. Park,Elena Mead,Steven Z. Pavletic,William Y. Go,Lamis K. Eldjerou,Rebecca Gardner,Noelle V. Frey,Kevin J. Curran,Karl S. Peggs,Marcelo C. Pasquini,John F. DiPersio,Marcel R.M. van den Brink,Krishna V. Komanduri,Stephan A. Grupp,Sattva S. Neelapu +21 more
TL;DR: The goal is to provide a uniform consensus grading system for CRS and neurotoxicity associated with immune effector cell therapies, for use across clinical trials and in the postapproval clinical setting.
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Chimeric Antigen Receptor Therapy.
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References
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“MIATA”—Minimal Information about T Cell Assays
Sylvia Janetzki,Cedrik M. Britten,Michael Kalos,Hyam I. Levitsky,Holden T. Maecker,C. J. M. Melief,Lloyd J. Old,Pedro Romero,Axel Hoos,Mark M. Davis +9 more
TL;DR: There are currently no standards for reporting results of vaccine testing in patients with a variety of tumor types and chronic viral diseases, and yet the best way to assess the clinical potential of these vaccines is to monitor the induced T cell response, so this letter is an effort to address this problem.
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Durable Remissions in Children with Relapsed/Refractory ALL Treated with T Cells Engineered with a CD19-Targeted Chimeric Antigen Receptor (CTL019)
Stephan A. Grupp,Stephan A. Grupp,Shannon L. Maude,Shannon L. Maude,Pamela A. Shaw,Richard Aplenc,Richard Aplenc,David M. Barrett,David M. Barrett,Colleen Callahan,Simon F. Lacey,Bruce L. Levine,J. Joseph Melenhorst,Laura S Motley,Susan R. Rheingold,Susan R. Rheingold,David T. Teachey,David T. Teachey,Patricia A. Wood,David L. Porter,Carl H. June +20 more
TL;DR: CTL019 cells can undergo robust in vivo expansion and can persist for 3 years or longer in children and young adults with r/r ALL, allowing for the possibility of long-term disease control without subsequent therapy such as SCT.
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Sustained remissions with CD19-specific chimeric antigen receptor (CAR)-modified T cells in children with relapsed/refractory ALL.
Shannon L. Maude,David T. Teachey,Susan R. Rheingold,Pamela A. Shaw,Richard Aplenc,David M. Barrett,Christine Barker,Colleen Callahan,Noelle V. Frey,Farzana Nazimuddin,Simon F. Lacey,Zhaohui Zheng,Bruce L. Levine,J. Joseph Melenhorst,Laura S Motley,David L. Porter,Carl H. June,Stephan A. Grupp +17 more
TL;DR: Of 59 patients aged 20mo-24y with CD19+ ALL, 44 had detectable disease prior to CTL019 cell infusion, while 15 were MRD-.
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Long-Term Outcomes Following CD19 CAR T Cell Therapy for B-ALL Are Superior in Patients Receiving a Fludarabine/Cyclophosphamide Preparative Regimen and Post-CAR Hematopoietic Stem Cell Transplantation
Daniel W. Lee,Maryalice Stetler-Stevenson,Constance M. Yuan,Nirali N. Shah,Cindy Delbrook,Bonnie Yates,Hua Zhang,Ling Zhang,James N. Kochenderfer,Steven A. Rosenberg,Terry J. Fry,David F. Stroncek,Crystal L. Mackall +12 more
TL;DR: Outcomes from a completed clinical trial of 53 children and young adults with relapsed/refractory ALL and 6 subjects with CNS ALL were rendered into CNS1 status with resolution of leptomeningeal enhancement, where appropriate, and CAR cells in CSF.
Journal ArticleDOI
Analysis of a Global Registration Trial of the Efficacy and Safety of CTL019 in Pediatric and Young Adults with Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)
Stephan A. Grupp,Theodore W. Laetsch,Jochen Buechner,Henrique Bittencourt,Shannon L. Maude,Shannon L. Maude,Michael R. Verneris,G.D. Myers,Michael Boyer,Susana Rives,Barbara De Moerloose,Eneida R. Nemecek,Krysta Schlis,Paul L. Martin,Muna Qayed,Peter Bader,Hidefumi Hiramatsu,Francoise Mechinaud,Gregory A. Yanik,Christina Peters,Andrea Biondi,André Baruchel,Nicolas Boissel,Joerg Krueger,Joerg Krueger,Carl H. June,Kapildeb Sen,Yiyun Zhang,Karen Thudium,Patricia A. Wood,Tetiana Taran,Michael A. Pulsipher +31 more
TL;DR: This pivotal global study in pediatric and young adult patients with r/r B-ALL receiving CTL019 confirms a high level of efficacy and a similar safety profile to that shown in the prior single center experience.
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