Humanized CD19 chimeric antigen receptor (CAR) T-cell therapy for high-risk and post-CAR relapse of B-cell acute lymphoblastic leukemia

作者：Lucy E. Cain, Yimei Li, Hongyan Liu, Shannon Christensen, Regina M. Myers, Allison Barz Leahy, Caroline Diorio, Nancy L. Shapiro, Elizabeth A. McBride, Colleen Callahan, Diane Baniewicz, Amanda M. DiNofia, Susan R. Rheingold, Lisa Wray, Stephen P. Hunger, Richard Aplenc, Susan McClory, Mackenzie Stewart, Gerald Wertheim, Andrew D. Fesnak, Gabriela Plesa, Don L. Siegel, Joseph A. Fraietta, Vanessa Gonzalez, Caitlin Hopkins, Amy Marshall, Amanda Kotch, Bruce L. Levine, Anne Chew, Elizabeth O. Hexner, Carl H. June, Stephan A. Grupp, Shannon L. Maude · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-646 · 被引用次数：1 · 研究领域：CAR-T cell therapy research、Acute Lymphoblastic Leukemia research、CRISPR and Genetic Engineering

Abstract Background CD19-directed chimeric antigen receptor T-cell (CART19) therapy has transformed the treatment landscape for relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). Yet relapse occurs in approximately 50% of recipients. These patients and subgroups of pediatric patients in first relapse, currently ineligible for commercial CART19, have very poor outcomes with current approaches, warranting investigation of alternative strategies. We previously investigated a humanized CART19 (huCART19) in a Phase I trial with encouraging responses in both CAR-naïve and CAR-exposed cohorts (Myers JCO 2021). Here we report outcomes from a Phase II clinical trial (NCT03792633) of huCART19 for high risk r/r B-ALL, including early bone marrow (BM) relapse, a subgroup with historically poor outcomes despite intensive therapy. Methods Patients aged 0-29 years (y) with CD19+ B-ALL were eligible in 2 cohorts: CAR-naïve patients with B-ALL that is refractory, in high risk first relapse, second or greater relapse, or relapsed after or ineligible for hematopoietic stem cell transplant (HSCT); CAR-exposed patients with poor response to prior cell therapy. Patients received huCART19 at a dose of 5x106 CAR T cells/kg (maximum 2.5x108) after lymphodepletion (LD) with fludarabine and cyclophosphamide. Response was assessed on day 28 by BM and cerebrospinal fluid morphology, minimal residual disease (MRD) by flow cytometry, and biologic response by B cell aplasia (BCA). The pr...