Chimeric Antigen Receptor-T Cells in the Modern Era of Chronic Lymphocytic Leukemia Treatment
1
Department of Pharmacy, University of Washington, Seattle, WA 98195, USA
2
Division of Hematology and Medical Oncology, University of Washington, Seattle, WA 98195, USA
3
Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
*
Author to whom correspondence should be addressed.
Cancers 2025, 17(2), 268; https://doi.org/10.3390/cancers17020268
Submission received: 28 November 2024
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Revised: 10 January 2025
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Accepted: 14 January 2025
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Published: 15 January 2025
(This article belongs to the Special Issue Updates in Chronic Lymphocytic Leukemia: 10 Years of Paradigm Change and Outlook for the Future)
Simple Summary
Common medications used to treat newly diagnosed and relapsed/refractory chronic lymphocytic leukemia (CLL) include Bruton tyrosine kinase inhibitors (BTKi) and B-cell lymphoma-2 inhibitors (BCL-2). However, once patients exhaust both options, there are a limited number of effective therapies. Chimeric antigen receptor (CAR)-T cells have become a widely used treatment modality in several B-cell malignancies and are newly being used to treat CLL. Here, we discuss the data supporting the new US Food and Drug Administration-approved CAR-T cell product for CLL, limitations of this treatment approach, and directions for future research.
Abstract
Pathway inhibitors targeting Bruton tyrosine kinase (BTK) and B-cell lymphoma-2 (BCL-2) have dramatically changed the treatment landscape for both treatment-naïve and relapsed/refractory chronic lymphocytic leukemia (CLL). However, with increased utilization, a growing number of patients will experience progressive disease on both agents. This subgroup of “double refractory” patients has limited treatment options and poor prognosis. Chimeric antigen receptor (CAR)-T cells have transformed the treatment of relapsed/refractory B-cell malignancies. Although the earliest success of CAR-T cell therapy was in CLL, the clinical application of this modality has lagged until the recent approval of the first CAR-T cell product for CLL. In this review, we describe the current treatment options for upfront and subsequent therapies and the unmet need for novel agents highlighted by the burgeoning role and challenges of CAR-T cell therapy.
