Humanized CD19-Targeted Chimeric Antigen Receptor (CAR) T Cells in CAR-Naive and CAR-Exposed Children and Young Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia

Authors

Regina M. Myers

¹Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA

Regina M. Myers, Yimei Li, Allison Barz Leahy, David M. Barrett, David T. Teachey, Colleen Callahan, Christina C. Fasano, Susan R. Rheingold, Amanda DiNofia, Lisa Wray, Richard Aplenc, Diane Baniewicz, Hongyan Liu, Pamela A. Shaw, Edward Pequignot, Kelly D. Getz, Jennifer L. Brogdon, Andrew D. Fesnak, Donald L. Siegel, Megan M. Davis, Chelsie Bartoszek, Simon F. Lacey, Elizabeth O. Hexner, Anne Chew, Gerald B. Wertheim, Bruce L. Levine, Carl H. June, Stephan A. Grupp, Shannon L. Maude

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PURPOSE

CD19-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.

We 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.

Seventy-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.

HuCART19 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.