As reported by Turtle et al in the Journal of Clinical Oncology, anti-CD19 chimeric antigen receptor–modified (CAR) T-cell therapy produced high response rates in patients with chronic lymphocytic leukemia previously treated with ibrutinib (Imbruvica).
In the phase I/II study, 24 patients received lymphodepleting chemotherapy and anti-CD19 CAR T cells at 2 x 105, 2 x 106, or 2 x 107 CAR T cells/kg in a single infusion. A total of 19 patients had disease progression on ibrutinib, 3 were ibrutinib intolerant, and 2 did not have disease progression on ibrutinib. Six patients were refractory to venetoclax (Venclexta), and 23 had a complex karyotype or 17p deletion.
At 4 weeks after CAR T-cell infusion, response on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria was achieved in 17 patients (71%). Cytokine-release syndrome occurred in 20 patients (83%), with 18 having grade 1 or 2 toxicity. Neurotoxicity occurred in 8 patients (33%), with 1 patient dying and all other cases being reversible.
Among the 20 patients receiving CAR T cells at or below the maximum tolerated dose of 2 x 106 cells/kg, 19 were restaged. Among them, response was achieved in 14 patients (74%), including a complete response in 4 (21%) and a partial response in 10 (53%); 15 of 17 patients (88%) with marrow disease before CAR T-cell treatment had no disease on flow cytometry.
Deep immunoglobulin heavy chain (IGH) sequencing in 12 of these patients showed no malignant sequences in marrow in 7 (58%). These patients had had 100% progression-free and overall survival at a median follow up of 6.6 months. Among the 19 restaged patients, median progression-free and overall survival was 9.8 months and not reached among those with a complete response and not reached and not reached among those with a partial response. Progression-free and overall survival were similar among patients with lymph node partial response or complete response.
The investigators concluded: “CD19 CAR T cells are highly effective in high-risk patients with [chronic lymphocytic leukemia] after they experience treatment failure with ibrutinib therapy.”
The study was supported by the National Cancer Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Life Science Discovery Fund, the Bezos Family, the University of British Columbia Clinical Investigator Program, and Juno Therapeutics.
Cameron J. Turtle, PhD, of Fred Hutchinson Cancer Research Center, is the corresponding author of the Journal of Clinical Oncology article.
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