Chimeric Antigen Receptor-T Cell Therapy for Lymphoma: New Settings and Future Directions

Simple Summary Despite the impressive efficacy of chimeric antigen receptor-T (CAR-T) cell therapy in the treatment of some subtypes of lymphomas, many patients are either not eligible or relapse after treatment. Thus, great efforts are being made to further improve the depth and durability of clinical responses, as well as to expand the settings in which CAR-T cells can be employed. The present review aims to summarize those efforts, offering an overview of recent advances and future perspectives in the field.Abstract In the last decade, anti-CD19 CAR-T cell therapy has led to a treatment paradigm shift for B-cell non-Hodgkin lymphomas, first with the approval for relapsed/refractory (R/R) large B-cell lymphomas and subsequently for R/R mantle cell and follicular lymphoma. Many efforts are continuously being made to extend the therapeutic setting in the lymphoma field. Several reports are supporting the safety and efficacy of CAR-T cells in patients with central nervous system disease involvement. Anti-CD30 CAR-T cells for the treatment of Hodgkin lymphoma are in development and early studies looking for the optimal target for T-cell malignancies are ongoing. Anti-CD19/CD20 and CD19/CD22 dual targeting CAR-T cells are under investigation in order to increase anti-lymphoma activity and overcome tumor immune escape. Allogeneic CAR product engineering is on the way, representing a rapidly accessible 'off-the-shelf' and potentially more fit product. In the present manuscript, we will focus on recent advances in CAR-T cell therapy for lymphomas, including new settings and future perspectives in the field, reviewing data reported in literature in the last decade up to October 2023.