Immunotherapy for multiple myeloma

Abstract

The potential potency of the immune system in targeting malignant plasma cells in multiple myeloma is best demonstrated in the allogeneic transplant setting, where durable responses can be achieved. However, allogeneic transplantation is associated with significant morbidity and mortality related to graft versus host disease, due to the non-specific nature of allo-reactive T cell responses mediated by donor lymphocytes. Immunotherapeutic approaches that more specifically target the malignant plasma cells have the potential to improve outcomes in multiple myeloma. The development of clinically efficacious immunotherapy in multiple myeloma is dependent on achieving a greater understanding of the complex interactions between the immunologic milieu and the growth of the malignant plasma cell clone. A number of antigens have been identified on malignant plasma cells that may be targeted by both humoral and cell mediated immunotherapeutic strategies. Encouraging results have been demonstrated both pre-clinically and in clinical trials. In this review, we summarize the clinical data evaluating immunotherapeutic approaches for the treatment of multiple myeloma.

Keywords::

• cellular immunotherapy
• dendritic cell vaccines
• NK cells

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Identifying unique antigens on myeloma cells that may be targeted by both cellular immunotherapy and antibodies.

• Developing strategies to present tumor antigens in the context of appropriate co-stimulation, in order to activate T cell responses and limit the development of anergy.

• A promising area of investigation lies in the developing antibodies that inhibit key pathways that blunt T cell activation.

• Overcoming tumor-associated immunosuppression and incorporating immunotherapy in settings of low disease burden is critical to optimizing the clinical benefit to immunotherapy.