Higher CART-19 Dosage More Effective at Inducing CR in Relapsed or Refractory CLL

Findings from a randomized, dose-optimization study of the long-term outcomes of anti-CD19 CAR T-cell therapy (CART-19) for relapsed or refractory chronic lymphocytic leukemia (CLL) has established a CART-19 dose that can induce complete response (CR) and extend progression-free survival in this setting (J Clin Oncol. 2020;38[25]:2862-2871).

The study was conducted by Noelle V. Frey, MD, MSCE, Associate Professor of Medicine, Hospital of the University of Pennsylvania, Philadelphia, and colleagues, between January 2013 and June 2016, and included 42 patients with relapsed or refractory CLL.

Of 38 patients infused with CART-19 therapy, 28 were initially randomized to receive a low (5×107) or high (5×108) dose. Ultimately, 24 of these patients were deemed evaluable for response assessment.

Following an interim analysis, an additional 10 patients received a higher dose of CART-19, including 8 who were evaluable for response. The median follow-up time frame was 31.5 months.

The 4-week CR and overall response rates for the 32 evaluable patients were 28% (90% CI, 16%-44%) for the low-dose group and 44% (90% CI, 29%-60%) for the high-dose group.

The median overall survival (OS) for all patients was 64 months; there was no statistically significant difference between the groups (P = .84). Prolonged survival was observed in patients who achieved a CR, regardless of the dose they received (P = .035), and a median OS was not reached in patients with CRs versus 64 months in those without CRs.

The median progression-free survival was 40.2 months in patients with CRs and 1 month in those without a CR (P <.0001). Toxicity was comparable between both dose groups.

“In patients with advanced CLL, a 5×108 dose of CART-19 may be more effective than 5×107 CART-19 at inducing CR without excessive toxicity,” Dr Frey and colleagues wrote.

“Attainment of a CR after CART-19 infusion, regardless of cell dose, is associated with longer OS and progression-free survival in patients with relapsed CLL,” they concluded.—Alexandra Graziano