Exploring the mechanisms of CD19 CAR T-cell failure and salvage strategies in B-cell lymphoma

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a potential treatment for patients with B-cell lymphoma in whom standard therapy has failed. The U.S. Food and Drug Administration (FDA) has approved anti-CD19 CAR T-cell products for B-cell lymphoma. However, growing experience has shown that treatment has limitations, such as relapses due to tumour mutations or CD19 antigen loss, unexpanded CAR T-cells, and/or poor persistence of CAR T-cells. Understanding the limitations of CAR T-cell therapy is essential to achieve the full potential of this therapeutic strategy. In this review, we analyse factors potentially affecting the efficacy of CAR T-cell therapy, explore the mechanisms of resistance to CD19 CAR T-cell therapy in B-cell lymphoma, and summarise potential strategies to overcome treatment barriers.