Autologous CD33-CAR-T cells for treatment of relapsed/refractory acute myelogenous leukemia.
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ABSTRACT:
SUBMITTER: Tambaro FP
PROVIDER: S-EPMC8550958 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
Publications
Autologous CD33-CAR-T cells for treatment of relapsed/refractory acute myelogenous leukemia.
Tambaro Francesco Paolo FP Singh Harjeet H Jones Emily E Rytting Michael M Mahadeo Kris M KM Thompson Philip P Daver Naval N DiNardo Courtney C Kadia Tapan T Garcia-Manero Guillermo G Chan Tim T Shah Rutul R RR Wierda William G WG
Leukemia 20210408 11
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Project description:PurposeCD19-targeted chimeric antigen receptor (CAR)-modified T cells demonstrate unprecedented responses in B-cell acute lymphoblastic leukemia (B-ALL); however, relapse remains a substantial challenge. Short CAR T-cell persistence contributes to this risk; therefore, strategies to improve persistence are needed.MethodsWe conducted a pilot clinical trial of a humanized CD19 CAR T-cell product (huCART19) in children and young adults with relapsed or refractory B-ALL (n = 72) or B-lymphoblastic lymphoma (n = 2), treated in two cohorts: with (retreatment, n = 33) or without (CAR-naive, n = 41) prior CAR exposure. Patients were monitored for toxicity, response, and persistence of huCART19.ResultsSeventy-four patients 1-29 years of age received huCART19. Cytokine release syndrome developed in 62 (84%) patients and was grade 4 in five (6.8%). Neurologic toxicities were reported in 29 (39%), three (4%) grade 3 or 4, and fully resolved in all cases. The overall response rate at 1 month after infusion was 98% (100% in B-ALL) in the CAR-naive cohort and 64% in the retreatment cohort. At 6 months, the probability of losing huCART19 persistence was 27% (95% CI, 14 to 41) for CAR-naive and 48% (95% CI, 30 to 64) for retreatment patients, whereas the incidence of B-cell recovery was 15% (95% CI, 6 to 28) and 58% (95% CI, 33 to 77), respectively. Relapse-free survival at 12 and 24 months, respectively, was 84% (95% CI, 72 to 97) and 74% (95% CI, 60 to 90) in CAR-naive and 74% (95% CI, 56 to 97) and 58% (95% CI, 37 to 90) in retreatment cohorts.ConclusionHuCART19 achieved durable remissions with long-term persistence in children and young adults with relapsed or refractory B-ALL, including after failure of prior CAR T-cell therapy.
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