The Latest Advances in CAR T-Cell Therapy for Refractory and Relapsed Lymphomas and Leukemias
H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
Author’s disclosures of potential conflicts of interest are found at the end of this article.
Marco L. Davila, MD, PhD, Department of Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612. E-mail: Marco.Davila@moffitt.org
J Adv Pract Oncol 2017;8:3–13 | https://doi.org/10.6004/jadpro.2017.8.6.10 | © 2017 Harborside Press®
ABSTRACT
While many patients with B-cell leukemias and lymphomas respond to therapy, those with relapsed or refractory disease often have poor outcomes and need more effective treatment options. The clinical development of tumor-targeted chimeric antigen receptor (CAR)–modified T cells has demonstrated the potential of this therapy for such difficult-to-treat hematologic malignancies. CAR T-cell therapies can be directed against the CD19 B-cell antigen, which is expressed on many leukemias and lymphomas. This article discusses the design of first- and second-generation CARs and their proposed mechanism of action. Recent clinical trial results in patients with relapsed or refractory B-cell malignancies treated with CD19-targeted, CAR-modified T cells are presented, including factors that may affect efficacy. The article also discusses key associated toxicities including cytokine-release syndrome, neurologic toxicities, and B-cell aplasia, as well as recommendations on management of these adverse events. As clinical use of this technology progresses, advanced practitioners will need to understand the biology underlying CAR T-cell therapy and be aware of its growing role in the treatment of relapsed/refractory leukemias and lymphomas. Advanced practitioners will also play crucial roles in identifying individuals at risk for treatment-related toxicities, grading adverse events, and managing toxicities.
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