Novel Treatments for Mantle Cell Lymphoma: From Targeted Therapies to CAR T Cells

Mantle cell lymphoma is a rare B-cell non-Hodgkin’s lymphoma that retains a sobering prognosis despite an extensive research effort. Mantle cell lymphoma remains incurable even with aggressive, and at times toxic, chemoimmunotherapy with early incorporation of autologous stem cell transplantation. Given this, attention has turned to the use of targeted therapies addressing dysregulation of B-cell signaling pathways. Drugs such as immunomodulatory agents, proteasome inhibitors, and Bruton’s tyrosine kinase inhibitors have shown success in the relapsed/refractory population, and there is ongoing investigation into the utilization of novel Bruton’s tyrosine kinase, B-cell leukemia/lymphoma-2, and spleen tyrosine kinase inhibitors alone or in combination in both the front-line and relapsed settings. Other areas of research in novel immunotherapies include investigations of bispecific T-cell engagers and antibody-drug conjugates. Most recently, chimeric antigen receptor T-cell therapy has been granted US Food and Drug Administration approval as a result of durable remissions even in high-risk patients who have classically done poorly with traditional chemoimmunotherapy. The intent of this article is to review the literature describing these selective therapies and discuss their current and future roles in the treatment of mantle cell lymphoma.