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
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
Citations
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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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Decreased Rates of Severe CRS Seen with Early Intervention Strategies for CD19 CAR-T Cell Toxicity Management
Rebecca Gardner,Rebecca Gardner,Kasey J. Leger,Colleen Annesley,Corinne Summers,Corinne Summers,Corinne Summers,Julie Rivers,Juliane Gust,Katherine Tarlock,Todd M. Cooper,Navin R. Pinto,Olivia Finney,Hannah Smithers,Assaf P. Oron,Daniel Li,Julie R. Park,Julie R. Park,Michael C. Jensen,Michael C. Jensen +19 more
TL;DR: Early intervention with immunomodulation appears to decrease the rates of sCRS while preserving the high rates of MRD-negative CR.
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Safety and Response of Incorporating CD19 Chimeric Antigen Receptor T Cell Therapy in Typical Salvage Regimens for Children and Young Adults with Acute Lymphoblastic Leukemia
Daniel W. Lee,Maryalice Stetler-Stevenson,Constance M. Yuan,Terry J. Fry,Nirali N. Shah,Cindy Delbrook,Bonnie Yates,Hua Zhang,Ling Zhang,James N. Kochenderfer,Steven A. Rosenberg,David F. Stroncek,Crystal L. Mackall +12 more
TL;DR: The results demonstrate that CD19 CAR T cell therapy is safe and effective with aggressive supportive care and use of an early intervention algorithm to prevent severe CRS and provides a potential for cure in primary refractory ALL.
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CR rates in relapsed/refractory (R/R) aggressive B-NHL treated with the CD19-directed CAR T-cell product JCAR017 (TRANSCEND NHL 001).
Jeremy S. Abramson,Maria Lia Palomba,Leo I. Gordon,Matthew A. Lunning,Jon E. Arnason,Andres Forero-Torres,Michael Wang,Tina Albertson,Tara Allen,Claire L. Sutherland,Benhuai Xie,Jacob Garcia,Tanya Siddiqi +12 more
TL;DR: JCAR017 is a second-generation, CD19-directed, 4-1BB CAR T cell product comprising CD8 and CD4 CAR T cells in a 1:1 ratio.
Journal ArticleDOI
CD19CAR T Cell Products of Defined CD4:CD8 Composition and Transgene Expression Show Prolonged Persistence and Durable MRD-Negative Remission in Pediatric and Young Adult B-Cell ALL
Rebecca Gardner,Rebecca Gardner,Olivia Finney,Hannah Smithers,Kasey J. Leger,Colleen Annesley,Corinne Summers,Corinne Summers,Corinne Summers,Christopher Brown,Stephanie Mgebroff,Catherine G. Lindgren,Karen Spratt,Assaf P. Oron,Daniel Li,Marie Bleakley,Julie R. Park,Julie R. Park,Michael C. Jensen,Michael C. Jensen,Michael C. Jensen +20 more
TL;DR: It is found it is feasible to generate CAR products from each of the enrolled subjects, and the durability of remission is highly influenced by the functional persistence of CAR-T cells.
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High Rates of Minimal Residual Disease-Negative (MRD−) Complete Responses (CR) in Adult and Pediatric and Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia (R/R ALL) Treated With KTE-C19 (Anti-CD19 Chimeric Antigen Receptor [CAR] T Cells): Preliminary Results of the ZUMA-3 and ZUMA-4 Trials
Bijal D. Shah,Van Huynh,Leonard S. Sender,Daniel W. Lee,Januario E. Castro,William G. Wierda,Andrew C. Dietz,Gary J. Schiller,Marie José Kersten,Rupert Handgretinger,Patrick Brown,Lia Gore,Nicola Gökbuget,Joseph Rosenthal,Marianna Sabatino,Adrian Bot,John M. Rossi,Yizhou Jiang,Lynn Navale,Shanna Stout,Jeff Aycock,Jeff Wiezorek,Rajul K. Jain,Alan S. Wayne +23 more
TL;DR: Shah et al. as discussed by the authors presented a preliminary analysis of the phase 1 portions of the multicenter ZUMA-1 trial, which to date have enrolled adult and pediatric patients, respectively with high leukemic burden (M3 marrow).
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