Evidence published in the Journal of Clinical Oncology demonstrates that anti-CD19 chimeric antigen receptor-modified T (CAR-T) cell therapy is highly effective in treating high-risk patients with chronic lymphocytic leukemia (CLL) previously treated with ibrutinib.1

High-risk patients with CLL are aggressively treated and experience high overall response rates (ORR). Yet these patients have low rates of complete response (CR) and overall survival (OS), and frequently relapse. Previous studies demonstrated that lymphodepletion therapy followed by CD10 CAR-T therapy produces high response rates and durable remissions.

For this study (ClinicalTrials.gov Identifier: NCT01865617), researchers assigned 24 patients with CLL who failed or progressed after ibrutinib therapy to receive lymphodepletion chemotherapy followed by CAR-T cell doses of 2 x 105, 2 x 106, or 2 x 107 CAR-T cells/kg. The primary outcome was safety and feasibility.

The overall response rate (CR and/or partial response [PR]) was 71% after 4 weeks of CAR-T cell infusion therapy.

Reversible cytokine release syndrome was observed in 83% of patients and neurotoxicity was observed in 33% of patients, leading to 1 death.

Twenty of 24 patients received lymphodepletion therapy and CAR-T cells below or at the maximum tolerated dose. Nineteen of these patients had an ORR of 74%. Seventeen patients presented with marrow disease prior to therapy, and 15 had no marrow disease after CAR-T cells as evidenced by flow cytometry.

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Deep IGH sequencing was performed for 12 patients, and 7 patients had no detectable malignant IGH sequences in the marrow post CAR-T therapy. Patients with CLL without malignant IGH clones in the marrow were associated with 100% progression-free survival (PFS) and OS during an average follow-up of 6.6 months.

These results show that CAR-T cells are tolerable and highly effective in the treatment of high-risk patients with CLL who fail ibrutinib therapy. 

Reference

  1. Turtle CJ, Hay KA, Hanafi LA, et al. Durable molecular remissions in chronic lymphocytic leukemia treated with CD19-specific chimeric antigen receptor-modified T cells after failure of ibrutinib. J Clin Oncol. 2017 Jul 17. doi: 10.1200/JCO.2017.72.8519 [Epub ahead of print]