[HTML][HTML] Durable molecular remissions in chronic lymphocytic leukemia treated with CD19-specific chimeric antigen receptor–modified T cells after failure of ibrutinib
Journal of Clinical Oncology, 2017•ncbi.nlm.nih.gov
Purpose We evaluated the safety and feasibility of anti-CD19 chimeric antigen receptor–
modified T (CAR-T) cell therapy in patients with chronic lymphocytic leukemia (CLL) who
had previously received ibrutinib. Methods Twenty-four patients with CLL received
lymphodepleting chemotherapy and anti-CD19 CAR-T cells at one of three dose levels (2×
10 5, 2× 10 6, or 2× 10 7 CAR-T cells/kg). Nineteen patients experienced disease
progression while receiving ibrutinib, three were ibrutinib intolerant, and two did not …
modified T (CAR-T) cell therapy in patients with chronic lymphocytic leukemia (CLL) who
had previously received ibrutinib. Methods Twenty-four patients with CLL received
lymphodepleting chemotherapy and anti-CD19 CAR-T cells at one of three dose levels (2×
10 5, 2× 10 6, or 2× 10 7 CAR-T cells/kg). Nineteen patients experienced disease
progression while receiving ibrutinib, three were ibrutinib intolerant, and two did not …
Abstract
Purpose
We evaluated the safety and feasibility of anti-CD19 chimeric antigen receptor–modified T (CAR-T) cell therapy in patients with chronic lymphocytic leukemia (CLL) who had previously received ibrutinib.
Methods
Twenty-four patients with CLL received lymphodepleting chemotherapy and anti-CD19 CAR-T cells at one of three dose levels (2× 10 5, 2× 10 6, or 2× 10 7 CAR-T cells/kg). Nineteen patients experienced disease progression while receiving ibrutinib, three were ibrutinib intolerant, and two did not experience progression while receiving ibrutinib. Six patients were venetoclax refractory, and 23 had a complex karyotype and/or 17p deletion.
Results
Four weeks after CAR-T cell infusion, the overall response rate (complete response [CR] and/or partial response [PR]) by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria was 71%(17 of 24). Twenty patients (83%) developed cytokine release syndrome, and eight (33%) developed neurotoxicity, which was reversible in all but one patient with a fatal outcome. Twenty of 24 patients received cyclophosphamide and fludarabine lymphodepletion and CD19 CAR-T cells at or below the maximum tolerated dose (≤ 2× 10 6 CAR-T cells/kg). In 19 of these patients who were restaged, the overall response rate by IWCLL imaging criteria 4 weeks after infusion was 74%(CR, 4/19, 21%; PR, 10/19, 53%), and 15/17 patients (88%) with marrow disease before CAR-T cells had no disease by flow cytometry after CAR-T cells. Twelve of these patients underwent deep IGH sequencing, and seven (58%) had no malignant IGH sequences detected in marrow. Absence of the malignant IGH clone in marrow of patients with CLL who responded by IWCLL criteria was associated with 100% progression-free survival and overall survival (median 6.6 months follow-up) after CAR-T cell immunotherapy. The progression-free survival was similar in patients with lymph node PR or CR by IWCLL criteria.
Conclusion
CD19 CAR-T cells are highly effective in high-risk patients with CLL after they experience treatment failure with ibrutinib therapy.
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