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.
