Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia
Jae H. Park,Isabelle Riviere,Mithat Gonen,Xiuyan Wang,Brigitte Senechal,Kevin J. Curran,Craig S. Sauter,Yongzeng Wang,Bianca Santomasso,Elena Mead,Mikhail Roshal,Peter Maslak,Marco L. Davila,Renier J. Brentjens,Michel Sadelain +14 more
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TLDR
A phase 1 trial involving adults with relapsed B‐cell ALL who received an infusion of autologous T cells expressing the 19‐28z CAR at the Memorial Sloan Kettering Cancer Center found that patients with a low disease burden before treatment had markedly enhanced remission duration and survival and had a markedly lower incidence of the cytokine release syndrome and neurotoxic events after infusion.Abstract:
Background CD19-specific chimeric antigen receptor (CAR) T cells induce high rates of initial response among patients with relapsed B-cell acute lymphoblastic leukemia (ALL) and long-term remissions in a subgroup of patients. Methods We conducted a phase 1 trial involving adults with relapsed B-cell ALL who received an infusion of autologous T cells expressing the 19-28z CAR at the Memorial Sloan Kettering Cancer Center (MSKCC). Safety and long-term outcomes were assessed, as were their associations with demographic, clinical, and disease characteristics. Results A total of 53 adults received 19-28z CAR T cells that were manufactured at MSKCC. After infusion, severe cytokine release syndrome occurred in 14 of 53 patients (26%; 95% confidence interval [CI], 15 to 40); 1 patient died. Complete remission was observed in 83% of the patients. At a median follow-up of 29 months (range, 1 to 65), the median event-free survival was 6.1 months (95% CI, 5.0 to 11.5), and the median overall survival was 12....read more
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References
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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
T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial
Daniel W. Lee,James N. Kochenderfer,Maryalice Stetler-Stevenson,Yongzhi K Cui,Cindy Delbrook,Steven A. Feldman,Terry J. Fry,Rimas J. Orentas,Marianna Sabatino,Nirali N. Shah,Seth M. Steinberg,Dave Stroncek,Nick Tschernia,Constance M. Yuan,Hua Zhang,Ling Zhang,Steven A. Rosenberg,Alan S. Wayne,Crystal L. Mackall +18 more
TL;DR: CD19-CAR T cell therapy is feasible, safe, and mediates potent anti-leukaemic activity in children and young adults with chemotherapy-resistant B-precursor acute lymphoblastic leukaemia and non-Hodgkin lymphoma.
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.
Journal ArticleDOI
CD19-Targeted T Cells Rapidly Induce Molecular Remissions in Adults with Chemotherapy-Refractory Acute Lymphoblastic Leukemia
Renier J. Brentjens,Marco L. Davila,Isabelle Riviere,Jae H. Park,Xiuyan Wang,Lindsay G. Cowell,Shirley Bartido,Jolanta Stefanski,Clare Taylor,Malgorzata Olszewska,Oriana Borquez-Ojeda,Jinrong Qu,Teresa Wasielewska,Qing He,Yvette Bernal,Ivelise Rijo,Cyrus V. Hedvat,Rachel Kobos,Kevin J. Curran,Peter G. Steinherz,Joseph G. Jurcic,Todd L. Rosenblat,Peter Maslak,Mark G. Frattini,Michel Sadelain +24 more
TL;DR: The results demonstrate the marked antitumor efficacy of 19-28z CAR-modified T cells in patients with relapsed/refractory B-ALL and the reliability of this therapy to induce profound molecular remissions, forming a highly effective bridge to potentially curative therapy with subsequent allo-HSCT.
Journal ArticleDOI
CD19 CAR–T cells of defined CD4+:CD8+ composition in adult B cell ALL patients
Cameron J. Turtle,Laïla Aïcha Hanafi,Carolina Berger,Ted Gooley,Sindhu Cherian,Michael Hudecek,Daniel Sommermeyer,Katherine Melville,Barbara S. Pender,Tanya M Budiarto,Emily Robinson,Natalia N Steevens,Colette Chaney,Lorinda Soma,Xueyan Chen,Cecilia Yeung,Brent L. Wood,Daniel Li,Jianhong Cao,Shelly Heimfeld,Michael C. Jensen,Stanley R. Riddell,David G. Maloney +22 more
TL;DR: It is established that high CAR-T cell doses and tumor burden increase the risks of severe cytokine release syndrome and neurotoxicity, and serum biomarkers that allow testing of early intervention strategies in patients at the highest risk of toxicity are identified.
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