Search

Mantle cell lymphoma (MCL) is a type of lymphoid malignancy that is rare in Japan. MCL is refractory to conventional chemotherapy and has dismal outcomes. Nonetheless, the prognosis of MCL has gradually improved with the advent of autologous stem cell transplantation and BTK inhibitors. First-line therapies incorporating BTK inhibitors are currently under development, and are expected to further improve the prognosis. Nevertheless, subsets with poor prognosis have been identified, including p53 abnormalities (TP53 mutations or deletions), blastoid variant, high MIPI-c, and POD24, and these show resistance to conventional treatments including BTK inhibitors. To overcome these challenges, novel therapies such as CAR-T therapy and combination therapy with BTK and BCL2 inhibitors are being developed, and should soon become clinically available in Japan. The therapeutic landscape for MCL is evolving dynamically, and this article will discuss the future of MCL treatment strategies in Japan.

It has been 20 years since the clinical introduction of rituximab, a monoclonal anti-CD20 antibody. Rituximab combination chemotherapy has substantially improved the prognosis of nearly all B-cell malignancies. Twenty years following the clinical introduction of rituximab, the era of molecular targeted agents and development of novel molecular targeted agents, including monoclonal antibody based on the molecular pathology, has been promoted. In recent years, CAR-T therapy and immune checkpoint inhibitors have been introduced in the clinical practice of malignant lymphoma. On the other hand, there are many histopathological subtypes that cannot directly receive the benefits of immunotherapy, and sufficient improvement in the prognosis of these subtypes is not seen. Therefore, further elucidation of molecular pathology and development of novel molecular targeted agents are crucial for the improvement of their prognosis. In this review, molecular targeted agents introduced into clinical practice in recent years, which revolutionized the treatment of malignant lymphoma, and molecular targeted agents expected to be introduced in clinical practice in the near future are discussed.