| Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive B-cell lymphoma. Cluster of differentiation 19 (CD19)-directed chimeric antigen receptor T-cell (CAR-T) therapy has substantially changed the treatment landscape of relapsed or refractory DLBCL. However, early progression, relapse after a partial response, persistent minimal residual disease (MRD) positivity, and late relapse continue to limit its long-term benefit. Maintenance therapy after CAR-T therapy is not simply an extension of post-chemotherapy consolidation; instead, it should be considered within an integrated framework encompassing CAR-T-cell expansion and exhaustion, antigen escape, an immunosuppressive microenvironment, residual tumor clones, and late-onset immune toxicities. In recent years, lenalidomide, programmed cell death protein 1 (PD-1) inhibitors, chidamide, Bruton tyrosine kinase (BTK) inhibitors, the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax, the exportin 1 (XPO1) inhibitor selinexor, bispecific antibodies, antibody-drug conjugates, and MRD-guided interventions have emerged as major areas of investigation. Based on major registration studies, real-world data, and outcomes of subsequent treatment after CAR-T failure, this review discusses the biological rationale, target populations, clinical evidence, drug selection, safety considerations, stopping criteria, and future trial design for maintenance therapy after CAR-T therapy in patients with DLBCL, with the aim of informing strategies to improve the long-term efficacy of CAR-T therapy. |
