CD19 CAR-T cell therapy for relapsed or refractory diffuse large B cell lymphoma: Why does it fail?

Chimeric antigen receptor T (CAR-T) cell therapy is an effective treatment for relapsed or refractory diffuse large B cell lymphoma (DLBCL) with three CD19 targeting products now FDA-approved for this indication. However, up to 60% of patients ultimately progress or relapse following CAR-T cell therapy. Mechanisms of resistance to CAR-T cell therapy in patients with DLBCL are likely multifactorial and have yet to be fully elucidated. Determining patient, tumor and therapy-related factors that may predict an individual's response to CAR-T cell therapy requires on-going analysis of data from clinical trials and real-world experience in this population. In this review we will discuss the factors identified to-date that may contribute to failure of CAR-T cell therapy in achieving durable remissions in patients with DLBCL.