Third-Generation CAR T-Cells Demonstrate Survival Benefit, Low Toxicity in CLL

Findings from the first ever phase I/II investigator-initiated trial of escalating doses of third-generation chimeric antigen receptor (CAR) T-cells targeting CD19 in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) have been published in Leukemia.

“[Third-generation CAR T-cells] demonstrated encouraging efficacy and exceptionally low treatment-specific toxicity, presenting new treatment options for patients with relapsed or refractory CLL,” wrote lead trial author Patrick Derigs, MD, of Heidelberg University Hospital in Heidelberg, Germany.

The nine patients in the trial cohort each had CLL where two prior treatments had been unsuccessful, including at least one pathway inhibitor or allogeneic hematopoietic cell transplantation. They received third-generation CAR T-cells at dose levels ranging from 1×10⁶ cells/m² to 200×10⁶ cells/m².

By day 90 of the trial, six patients had attained complete response, five of whom had undetectable measurable residual disease. One patient experienced grade 3 cytokine release syndrome, but there were no instances of neurotoxicity in the cohort.

The cohort had a median follow-up of 27 months, with a calculated two-year progression-free survival rate of 30% and an overall survival rate of 69%.

“[Third-generation CAR T-cells] products of responders contained significantly more CD4+ T cells compared to non-responders. In non-responders, a strong enrichment of effector memory-like CD8+ T cells with high expression of CD39 and/or CD197 was observed,” Dr. Derigs noted.

Reference

Derigs P, Schubert ML, Dreger P, et al. Third-generation anti-CD19 CAR T cells for relapsed/refractory chronic lymphocytic leukemia: a phase 1/2 study. Leukemia. Published online August 27, 2024. doi:10.1038/s41375-024-02392-7