Targeting CD19 for diffuse large B cell lymphoma in the era of CARs: Other modes of transportation

CD19 is nearly ubiquitously expressed on B-lymphocytes and in B-cell malignancies. Although CD19-directed CAR T cells have greatly improved outcomes in B-cell malignancies, there are significant limitations with this therapy. CD19 can also be effectively targeted by other drug classes, such as monoclonal antibodies, antibody -drug conjugates, and bispecific T cell engagers or antibodies. However, the optimal patient selection and sequencing of these novel therapies has not yet been established. In this review, we discuss the utilization of CD19 as a target for the treatment of DLBCL, focusing on tafasitamab, loncastuximab tesirine, and blinatumo-mab. We provide a comprehensive review of the pivotal clinical trials, discussing the strength and limitations of the data for each agent. We explore the emerging evidence that CD19 expression is retained following exposure to these agents and that patients can be successfully re-challenged with anti-CD19 therapies of a different drug class upon disease relapse post-CAR T cells. Finally, we discuss how these drugs potentially fit into the most current treatment paradigm for DLBCL.

Automated summary

CD19 is widely present on B-lymphocytes and B-cell malignancies. CD19-directed CAR T cells have improved outcomes in B-cell malignancies, but there are limitations. CD19 can also be targeted by other drugs, but optimal patient selection and sequencing are not established. This review focuses on CD19 as a target for DLBCL treatment, discussing clinical trials of tafasitamab, loncastuximab tesirine, and blinatumo-mab, and the potential of re-challenging with anti-CD19 therapies post-CAR T cells.