CD19 CAR T-Cells Combined with Ibrutinib to Induce Complete Remission in CLL

Conference Correspondent - ASCO 2017 - Chronic Lymphocytic Leukemia

Immunotherapy with anti-CD19 chimeric antigen receptor (CAR) T-cells induces complete remission (CR) in the minority of patients with chronic lymphocytic leukemia (CLL), but when CR does occur, it tends to be durable. Having preclinical knowledge of synergy, investigators combined anti-CD19 CAR T-cells with ibrutinib to test the hypothesis that pre- and concurrent treatment would enhance the CR rate in this patient population.

This pilot trial of anti-CD19 CAR T-cells enrolled adults with CLL/small lymphocytic lymphoma who were not in CR despite ≥6 months of ibrutinib therapy. Patients must have failed at least 1 regimen before ibrutinib, unless they had del(17)(p13.1) or a TP53 mutation. Patients were lymphodepleted 1 week before infusion with humanized anti-CD19 CAR T-cells. Ibrutinib was continued throughout the trial.

Ten patients, 9 of whom were male, aged 47 to 77 years with 0 to 12 regimens prior to receiving ibrutinib, were infused. Various abnormalities of TP53 or ATM and increasing BTK C481S clones existed in the patients. Median marrow CLL burden was 10% (range, 10%-50%) with a median follow-up of 6 months (range, 0.5-9 months). Cytokine release syndrome developed in 9 patients. One patient developed grade 4 tumor lysis syndrome. At 3 months, 8 evaluable patients had achieved a minimal residual disease–negative marrow CR (89%). At last follow-up, all remained in marrow CR.

This study may support the use of CAR T-cells in combination with ibrutinib in patients with high-risk CLL. Longer follow-up will be needed to confirm the durability of these results. Plans are to treat 25 patients.

Gill S, et al. ASCO Abstract 7509.

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Last modified: June 8, 2017
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