The Cancer-Immunity Cycle in Multiple Myeloma

Abstract

Multiple myeloma is a plasma cell malignancy that primarily affects the elderly. The global burden of multiple myeloma is increasing in many countries due to an aging population. Despite recent advances in therapy, myeloma remains an incurable disease, highlighting the pressing need for new therapies. Accumulating evidence supports that triggering the host immune system is a critical therapeutic mechanism of action by various anti-myeloma therapies. These anti-myeloma therapies include proteasome inhibitors, immunomodulatory drugs, monoclonal antibody drugs, and autologous stem cell transplantation. More recently, T cell-based immunotherapeutics (including chimeric antigen receptor T-cell therapies and bispecific T-cell engagers) have shown dramatic clinical benefits in patients with relapsed or refractory multiple myeloma. While immune-based therapeutic approaches are recognized as key modalities for improved clinical outcomes in myeloma patients, understanding the immune system in multiple myeloma patients remains elusive. The cancer-immunity cycle is a conceptual framework illustrating how immune cells recognize and eliminate tumor cells. Based on this framework, this review will provide an overview of the immune system in multiple myeloma patients and discuss potential therapeutic approaches to stimulate anti-tumor immunity.

Keywords:

• multiple myeloma
• immune checkpoint
• immunotherapy
• immunosuppression

Acknowledgment

The authors appreciate Bianca Nowlan for critical reading and helpful suggestions. K.N. is supported by the Naito Foundation and NHMRC Project Grant (1159593). K.N. is a recipient of recipients of a Leukemia Foundation of Australia SERP grant. This project was supported by grant 2000538 awarded through the 2020 Priority-driven Collaborative Cancer Research Scheme and funded by the Leukaemia Foundation with the support of Cancer Australia.

Disclosure

The authors have no conflicts of interest to declare.