4.7 Editorial Material

Do CARs finally hit the CLL road?

Journal

BLOOD
Volume 139, Issue 12, Pages 1775-1776

Publisher

AMER SOC HEMATOLOGY
DOI: 10.1182/blood.2021014492

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This study summarizes a phase 1/2 dose-escalation chimeric antigen receptor T (CART) trial for patients with chronic lymphocytic leukemia (CLL). The CART19 cells treatment showed promising results, with most patients experiencing cytokine release syndrome and neurotoxicity, but achieving long-lasting complete responses and undetectable minimal residual disease in a subset of patients.
In this issue of Blood,1 Siddiqi et al summarize their phase 1/2 dose-escalation chimeric antigen receptor T (CART) trial for patients with chronic lymphocytic leukemia (CLL), including those who had failed prior ibrutinib treatment. Twenty-five patients with ibrutinib refractory/relapsed CLL/small lymphocytic lymphoma, enriched for high-risk features (half of the patients had complex karyotype and more than half had TP53 aberrations), received anti-CD19 CART19 cells following lymphodepleting chemotherapy. The CART19 product, lisocabtagene, consists of 2 separate infusions of sepa-rately activated, transduced, and expanded autologous CD4+ and CD8+ cells. Although most patients had cytokine release syndrome (CRS), 90% experienced mild disease. Neurotoxicity occurred in 40%, with half of these high grade. Complete responses were observed in 10 patients. Nine of these also had undetectable MRD (uMRD), which was achieved early after infusion. A clear association was observed between uMRD and duration of response: just 3 months in patients with MRD+ vs not reached in patients with uMRD. One-quarter of patients that progressed after CART19 cells had Richter transformation (RT). A follow-up phase study is currently underway.

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