CAR-T Cell Therapy Highly Effective in Some Patients with Leukemia

CD19 chimeric antigen receptor–modified T (CAR-T) cell therapy is safe and highly effective for treating patients with chronic lymphocytic leukemia (CLL) who are refractory to ibrutinib therapy, according to a recent study.

In their study, the researchers evaluated 24 patients with CLL. Each patient received lymphodepleting chemotherapy and 1 of 3 dose levels of anti-CD19 CAR-T cells: 2 × 10⁵ CAR-T cells/kg, 2 × 10⁶ CAR-T cells/kg, or 2 × 10⁷ CAR-T cells/kg. Median follow-up lasted 6.6 months.
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All 24 patients included in the study were refractory to ibrutinib, with 19 patients experiencing disease progression on ibrutinib, 3 being intolerant to the therapy, and 2 not experiencing disease progression on ibrutinib. Additionally, 6 patients were refractory to venetoclax, and 23 had a complex karyotype and/or 17p deletion.

Results indicated that the overall response rate was 71% (17 of 24 patients). This rate included complete response (CR) and partial response (PR) rates, as defined by the International Workshop on Chronic Lymphocytic Leukemia (IWCLL). A total of 23 (83%) patients developed cytokine release syndrome, and 8 (33%) developed neurotoxicity, which was reversible in all patients except 1, who had had a fatal outcome.

According to the researchers, 20 patients had received cyclophosphamide and fludarabine lymphodepletion, and CD19 CAR-T cells at or below the maximum tolerated dose (2 × 10⁶ CAR-T cells/kg or lower). After 19 of these patients were restaged, the overall response rate was 74% at 4 weeks post-infusion.

A total of 15 of 17 (88%) patients with marrow disease before CAR-T cells had no disease by flow cytometry after CAR-T cells. A total of 12 patients had undergone deep IGH sequencing, and 7 (58%) had no malignant IGH sequences detected in their marrow. The researchers found that the absence of the malignant IGH clone in marrow of patients who responded to the treatment was associated with 100% progression-free survival and overall survival after CAR-T cell immunotherapy. This progression-free survival was similar in patients with lymph node PR or CR.

“CD19 CAR-T cells are highly effective in high-risk patients with CLL after they experience treatment failure with ibrutinib therapy,” the researchers concluded.

—Christina Vogt

Reference:

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