Highlights: Immunotherapy for B-cell lymphoma

Remarkable advances in cellular therapy, such as the development of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies (BsAbs), have recently been achieved. These advances have significantly improved survival outcomes for patients with malignant lymphoma and multiple myeloma (MM). Several formulations of anti-CD19 CAR T-cell therapy and BsAbs have been developed, and cellular therapy has been optimized for clinical practice for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and MM. Axicabtagene ciloleucel and lisocabtagene maraleucel have become the standard treatment options for patients with DLBCL who are refractory or who have relapsed to first-line therapy within one year after achieving complete remission, indicating that cell therapy is being introduced earlier.^1,2 BsAbs are also used in flexible treatment approaches. Clinical trials evaluating the combination therapies of BsAbs with noncytotoxic agents or nonchemotherapy drugs are currently underway for patients with relapsed or newly diagnosed mature B-cell lymphoma. Cell therapy will lead to a paradigm shift for treatment approaches for mature B-cell lymphoma and MM. In cell therapy, toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) have been observed. These toxicities are not experienced with conventional cytotoxic chemotherapy. BsAbs are more accessible treatment options than CAR T-cell therapy is because their administration is not restricted to specific institutions. Therefore, hematologists must understand these new toxicities and be able to manage them carefully. A deep understanding of the current status and future development of cell therapy is essential.

Here, the toxicity and management of CAR T-cell therapy, as well as recent advances in treatment outcomes for cell therapies that target DLBCL, FL, and MM, are reviewed. Goto H. discusses “CRS and ICANS in CAR T-cell therapy for large B-cell lymphoma” from the perspective of toxicity and management in CAR T-cell therapy for patients with large B-cell lymphoma (in press). Iriyama C. describes “Development and biomarkers of CD20/CD3 bispecific antibodies in diffuse large B cell lymphoma,” primarily on the basis of the results of extensive clinical trials, including the consideration of predictive biomarkers associated with the use of BsAbs (in press). Kobayashi T. describes “Chimeric antigen receptor T-cell and bispecific antibody therapies for follicular lymphoma: Recent advances and future prospects”, summarizing the recent clinical data on cellular immunotherapy for FL while incorporating comparative perspectives between CAR T-cell therapy and BsAbs (in press). Finally, Suzuki T. et al. describes “Advances and Future Perspectives in Chimeric Antigen Receptor T-cell and Bispecific Antibody Therapies for Multiple Myeloma”, summarizing the clinical data on cellular therapy for MM, including findings for a new cell therapy under development.³

This review series aims to summarize recent clinical advances in cell therapy for mature B-cell malignancies, with a focus on aspects that are relevant to clinical practice in hematology. In addition, potential future directions in this field are highlighted, and an overview of current approaches for toxicity management is provided.