How to integrate CD19 specific chimeric antigen receptor T cells with other CD19 targeting agents in diffuse large B‐cell lymphoma?

Abstract About one third of patients with diffuse large B‐cell lymphoma (DLBCL) have a relapsing/refractory (R/R) disease after first line chemo‐immunotherapy, with particularly poor outcomes observed in patients with primary refractory disease and early relapse. CD19 specific chimeric antigen receptor (CAR) T cell therapy is a game changer that results in durable and complete response rates in almost half of the patients with R/R DLBCL. Other emerging CD19‐targeting therapies include monoclonal antibodies, bispecific antibodies and targeting antibody‐drug conjugates, which also show encouraging results. However, the timing and sequencing of different anti‐CD19‐targeting agents and how they might interfere with subsequent CAR T cell treatment is still unclear. In this review, we summarize the results of the pivotal clinical trials as well as evidence from real‐world series of the use of different CD19‐targeting approved agents. We discuss the effect of various therapies on CD19 expression and its implications for treatment sequencing.