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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