Sequencing CD19-targeted therapies in patients with relapsed/refractory large B-cell lymphoma: A narrative review

CD19 is expressed on B cells from an early stage and in most B-cell malignancies, but not in hematopoietic stem cells or other normal tissues, thereby making it an attractive therapeutic target for the treatment of patients with relapsed or refractory (R/R) large B-cell lymphomas. While CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapies, monoclonal antibodies, and antibody-drug conjugates are effective therapies for B-cell lymphomas, outcomes in the R/R setting may depend on exposure to prior treatments with the same antigen. There are limited data on the impact of sequencing these treatment modalities. This review highlights recent trial and real-world data focusing on the efficacy and safety of the CD19-targeted agents tafasitamab-lenalidomide and loncastuximab tesirine before and after CAR-T therapy in patients with R/R B-cell lymphoma and addresses the importance of assessing pretreatment target antigen levels as well as identifying common molecular mechanisms of treatment failure. Additionally, this analysis discusses the unmet needs in patients with high-risk disease and the challenges of sequencing these therapeutic strategies, while providing expert clinical practice recommendations to optimize patient outcomes.