@article{95e8752428874baf895ec3a321eea8d8,
title = "KTE-X19 anti-CD19 CAR T-cell therapy in adult relapsed/refractory acute lymphoblastic leukemia: ZUMA-3 phase 1 results",
abstract = "ZUMA-3 is a phase 1/2 study evaluating KTE-X19, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in adult relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We report the phase 1 results. After fludarabine-cyclophosphamide lymphodepletion, patients received a single infusion of KTE-X19 at 2 × 106, 1 × 106, or 0.5 × 106 cells per kg. The rate of dose-limiting toxicities (DLTs) within 28 days after KTE-X19 infusion was the primary end point. KTE-X19 was manufactured for 54 enrolled patients and administered to 45 (median age, 46 years; range, 18-77 years). No DLTs occurred in the DLT-evaluable cohort. Grade ≥3 cytokine release syndrome (CRS) and neurologic events (NEs) occurred in 31% and 38% of patients, respectively. To optimize the risk-benefit ratio, revised adverse event (AE) management for CRS and NEs (earlier steroid use for NEs and tocilizumab only for CRS) was evaluated at 1 × 106 cells per kg KTE-X19. In the 9 patients treated under revised AE management, 33% had grade 3 CRS and 11% had grade 3 NEs, with no grade 4 or 5 NEs. The overall complete remission rate correlated with CAR T-cell expansion and was 83% in patients treated with 1 × 106 cells per kg and 69% in all patients. Minimal residual disease was undetectable in all responding patients. At a median follow-up of 22.1 months (range, 7.1-36.1 months), the median duration of remission was 17.6 months (95% confidence interval [CI], 5.8-17.6 months) in patients treated with 1 × 106 cells per kg and 14.5 months (95% CI, 5.8-18.1 months) in all patients. KTE-X19 treatment provided a high response rate and tolerable safety in adults with R/R B-ALL. Phase 2 is ongoing at 1 × 106 cells per kg with revised AE management. This trial is registered at www.clinicaltrials.gov as #NCT02614066.",
author = "Shah, {Bijal D.} and Bishop, {Michael R.} and Oluwole, {Olalekan O.} and Logan, {Aaron C.} and Baer, {Maria R.} and Donnellan, {William B.} and O'Dwyer, {Kristen M.} and Houston Holmes and Arellano, {Martha L.} and Armin Ghobadi and Pagel, {John M.} and Yi Lin and Cassaday, {Ryan D.} and Park, {Jae H.} and Mehrdad Abedi and Castro, {Januario E.} and DeAngelo, {Daniel J.} and Malone, {Adriana K.} and Raya Mawad and Schiller, {Gary J.} and Rossi, {John M.} and Adrian Bot and Tong Shen and Lovely Goyal and Jain, {Rajul K.} and Remus Vezan and Wierda, {William G.}",
note = "Funding Information: Conflict-of-interest disclosure: B.D.S. reports honoraria from Pharmacyclics, Janssen, Acrotech, Spectrum, BeiGene, and Gilead Sciences; a consultancy or advisory role for Adaptive Biotechnologies, Bristol Myers Squibb/Celgene, Novartis, Pfizer, Amgen, Precision Biosciences, and Kite, a Gilead Company; research funding from Incyte, Jazz Pharmaceuticals, Gilead Sciences, and Kite; and travel support from Celgene, Novartis, Pfizer, Janssen, Seattle Genetics, Stemline Therapeutics, and Kite. M.R. Bishop reports honoraria from Kite, Incyte, Celgene, Sanofi, Novartis, Bristol Myers Squibb, and Agios; a consulting or advisory role with Novartis, Kite, CRISPR Therapeutics, Agios, Iovance, Bluebird Bio, WindMil Therapeutics, and Acellx; speakers bureau service with Kite, Agios, Incyte, Sanofi, and Bristol Myers Squibb; research funding from Kite, Novartis, CRISPR Therapeutics, Arcellx, Autolus, Immatics, Triumvera, and Tmunity; and travel support from Kite, Novartis, Bristol Myers Squibb, Agios, and Incyte. O.O.O. reports a consultancy or advisory role for Kite, Pfizer, Spectrum Pharmaceuticals, Legend, and Bayer. A.C.L. reports a consultancy or advisory role for Amgen, Pfizer, Bristol Myers Squibb, Agios, Novartis, and Incyte; and research funding from Astellas, Jazz, Kite, Amphivena, Kadmon, Autolus, and Pharmacyclics. M.R. Baer reports research funding from the University of Maryland Greenebaum Comprehensive Cancer Center. H.H. reports a consultancy or advisory role for Kite, Gilead Sciences, Bayer, Rigel, Janssen, and Juno; speakers' bureau participation for Kite, Seattle Genetics, Rigel, Dova, and Karyo‐pharm, research funding from Kite, Unum, Juno, Novartis, Genentech, ADC Therapeutics, Seattle Genetics, Bluebird, Incyte, and Janssen; and patents, royalties, or other intellectual property from a pending patent. M.L.A. reports a consultancy or advisory role for Gilead Sciences and Kite and research funding from Emory University. A.G. reports a consulting or advisory role, honoraria, and research funding from Kite and a consulting and advisory role with Amgen, Atara, Wugen, and Celgene. J.M.P. reports a consultancy or advisory role for Kite, Pharmacyclics, and Actinium. Y.L. reports a consultancy or advisory role for Kite, Janssen, Novartis, Celgene, Bluebird Bio, Juno, Legend, Sorrento, Gamida Cells, and Vineti and research funding from Kite, Janssen, Celgene, Bluebird Bio, Merck, and Takeda. R.D.C. reports employment and stock or other ownership with Seagen; a consultancy or advisory role for Kite, Pfizer, and Amgen; and research funding from Pfizer, Merck, Amgen, Kite, and Vanda Pharmaceuticals. J.H.P. reports a consultancy or advisory role for Kite, Novartis, Amgen, InCyte, Allogene, Autolus, Artiva, Intellia, Servier, Pfizer, Takeda, and AstraZeneca and research funding from Genentech, Amgen, and Juno Therapeutics. M.A. reports consultancy or advisory role for Celgene, Kite, and Takeda, research funding from Amgen, Celgene, and CIRM, and speakers' bureau participation for Bristol Myers Squibb, AbbVie, Celgene, Gilead, Seattle Genetics, and Takeda. D.J.D. reports honoraria from Autolos, Agios, Blueprint, Forty-Seven, Incyte, Jazz, Kite, Novartis, Pfizer, Servier, and Takeda; research funding from AbbVie, Glycomimetics, Novartis, and Blueprint Pharmaceuticals; and travel support from Glycomimetics, Pfizer, and Blueprint Pharmaceuticals. G.J.S. reports speakers' bureau participation with Kite. A.B. reports employment with Kite, stock or other ownership in Gilead Sciences, a consultancy or advisory role with Gilead Sciences, and travel support from Gilead Sciences. T.S. reports employment, stock or other ownership, honoraria, and travel support with Kite. J.M.R. reports employment with Kite. L.G. reports employment with Kite, and stock or other ownership in Gilead. R.K.J. reports employment with Kite and Vida Ventures, stock or other ownership in Kite and Amgen, patents, royalties, or other intellectual property from CAR T field, and travel support from Kite. R.V. reports employment with Kite. W.G.W. reports consultancy or advisory role for Sanofi and Genzyme, and research funding from GlaxoSmithKline, Novartis, AbbVie, Genentech, Karyopharm, Pharmacyclics, Acerta, Gilead Sciences, Juno Therapeutics, Sunesis, Miragen, Oncternal Therapeutics, Cyclacel, Loxo Oncology, Janssen, and Xencor. The remaining authors declare no competing financial interests. Publisher Copyright: {\textcopyright} 2021 American Society of Hematology",
year = "2021",
month = jul,
day = "8",
doi = "10.1182/blood.2020009098",
language = "English (US)",
volume = "138",
pages = "11--22",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "1",
}