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Clinical Trial
. 2019 Dec 26;134(26):2361-2368.
doi: 10.1182/blood.2019001641.

Toxicity and Response After CD19-specific CAR T-cell Therapy in Pediatric/Young Adult Relapsed/Refractory B-ALL

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Free PMC article
Clinical Trial

Toxicity and Response After CD19-specific CAR T-cell Therapy in Pediatric/Young Adult Relapsed/Refractory B-ALL

Kevin J Curran et al. Blood. .
Free PMC article

Abstract

Chimeric antigen receptor (CAR) T cells have demonstrated clinical benefit in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We undertook a multicenter clinical trial to determine toxicity, feasibility, and response for this therapy. A total of 25 pediatric/young adult patients (age, 1-22.5 years) with R/R B-ALL were treated with 19-28z CAR T cells. Conditioning chemotherapy included high-dose (3 g/m2) cyclophosphamide (HD-Cy) for 17 patients and low-dose (≤1.5 g/m2) cyclophosphamide (LD-Cy) for 8 patients. Fifteen patients had pretreatment minimal residual disease (MRD; <5% blasts in bone marrow), and 10 patients had pretreatment morphologic evidence of disease (≥5% blasts in bone marrow). All toxicities were reversible, including severe cytokine release syndrome in 16% (4 of 25) and severe neurotoxicity in 28% (7 of 25) of patients. Treated patients were assessed for response, and, among the evaluable patients (n = 24), response and peak CAR T-cell expansion were superior in the HD-Cy/MRD cohorts, as compared with the LD-Cy/morphologic cohorts without an increase in toxicity. Our data support the safety of CD19-specific CAR T-cell therapy for R/R B-ALL. Our data also suggest that dose intensity of conditioning chemotherapy and minimal pretreatment disease burden have a positive impact on response without a negative effect on toxicity. This trial was registered at www.clinicaltrials.gov as #NCT01860937.

Conflict of interest statement

Conflict-of-interest disclosure: K.J.C. has received research support from Juno Therapeutics and Novartis and has consulted, served on advisory boards, and participated in educational seminars for Juno Therapeutics, Novartis, Gerson Lehrman Group (GLG), Geurson Medical Group, AXIS Education, and Omnicron Healthcare. S.P.M. has participated on advisory boards for Novartis. R.J.B., M.S., and I.R. are cofounders and receive royalties from Juno Therapeutics. C.S.S. has received research support from Juno Therapeutics and has consulted for or served on advisory boards of Juno Therapeutics, Kite, and Novartis. The remaining authors declare no competing financial interests.

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