CAR-T Cell Therapy for Chronic Lymphocytic Leukemia

Summary and Comment |
October 4, 2017

CAR-T Cell Therapy for Chronic Lymphocytic Leukemia

  1. Michael E. Williams, MD, ScM

This complex therapeutic modality was highly effective in relapsed CLL patients who failed treatment with ibrutinib.

  1. Michael E. Williams, MD, ScM

Chimeric antigen receptor-modified T (CAR-T) cells directed against the B-cell surface antigen CD19 have shown impressive activity in relapsed and refractory B-cell malignancies.

Now, investigators have conducted a partially funded, phase I–II study to assess the safety and feasibility of CD19 CAR-T cell therapy in heavily pretreated patients with chronic lymphocytic leukemia (CLL) who had failed ibrutinib. All but one patient had high-risk cytogenetics, five had Richter's transformation, and two had active central nervous system disease. Peripheral blood CD4+ and CD8+ T-cells were isolated and modified via a lentiviral vector, propagated in vitro, and then infused following lymphodepletion chemotherapy with cyclophosphamide and/or fludarabine.

Results were as follows:

  • 20 patients (83%) experienced cytokine release syndrome (CRS), 6 of whom required treatment with the anti-IL6 antibody tocilizumab plus corticosteroids.

  • Eight patients developed neurotoxicity, which was reversible in all but one patient.

  • 17 of 21 patients (81%) with baseline marrow involvement became marrow-negative at 4 weeks after CAR-T infusion, and 16 of 23 (70%) achieved nodal response by 4 weeks.

  • Six patients with persistent disease or subsequent relapse received a second cycle of lymphodepletion and CAR-T infusion; of these, two achieved complete remission.

Comment

This study and others confirm high efficacy and durable responses with this complex therapeutic modality in patients with CLL and B-cell lymphomas that are otherwise refractory to immunochemotherapy, ibrutinib, venetoclax, and other agents. As the technology to generate CAR-T cells and the management of CRS and neurotoxicity become more refined and available, there is optimism that more patients will be able to benefit from this powerful therapy.

Editor Disclosures at Time of Publication

  • Disclosures for Michael E. Williams, MD, ScM at time of publication Consultant / Advisory board Celgene; Gilead; Takeda; TG Therapeutics Speaker's bureau Research to Practice Grant / Research support Celgene; Janssen; Allos; Pharmacyclics; Gilead; Novartis; Takeda Editorial boards Annals of Lymphoma; Journal of Clinical Oncology; Blood; British Journal of Haematology; Haematologica; American Journal of Hematology Leadership positions in professional societies Lymphoma Research Foundation (Scientific Advisory Board); American Board of Internal Medicine (Chair, Hematology Subspecialty Board; Member, Council)

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