Chimeric antigen receptor T‐cell therapy for haematological malignancies: Insights from fundamental and translational research to bedside practice

Abstract

SummaryAutologous chimeric antigen receptor (CAR) T‐cell therapy has revolutionized the treatment of lymphoid malignancies, leading to the approval of CD19‐CAR T cells for B‐cell lymphomas and acute leukaemia, and more recently, B‐cell maturation antigen‐CAR T cells for multiple myeloma. The long‐term follow‐up of patients treated in the early clinical trials demonstrates the possibility for long‐term remission, suggesting a cure. This is associated with a low incidence of significant long‐term side effects and a rapid improvement in the quality of life for responders. In contrast, other types of immunotherapies require prolonged treatments or carry the risk of long‐term side effects impairing the quality of life. Despite impressive results, some patients still experience treatment failure or ultimately relapse, underscoring the imperative to improve CAR T‐cell therapies and gain a better understanding of their determinants of efficacy to maximize positive outcomes. While the next‐generation of CAR T cells will undoubtingly be more potent, there are already opportunities for optimization when utilizing the currently available CAR T cells. This review article aims to summarize the current evidence from clinical, translational and fundamental research, providing clinicians with insights to enhance their understanding and use of CAR T cells.