Adoptive Immunotherapy and High-Risk Myeloma

SIMPLE SUMMARY: Multiple myeloma is a cancer of the bone marrow which accounts for approximately 1.8% of all cancer diagnoses worldwide. The clinical outcomes for patients with multiple myeloma have significantly improved in the most recent decade, resulting in better quality of life and prolonged survival. However, this remains a largely incurable disease with inevitable relapse and resistance to medical treatment. Furthermore, there is a cohort of high-risk myeloma patients who possess disease characteristics which predispose them to worse clinical outcomes and poor response to treatment. There is a pressing need to develop new treatment strategies for myeloma, particularly therapeutic approaches which would be successful in high-risk patients. Recently there has been promising advances in cell-based immunological therapies for myeloma; however, further studies are needed to fully establish their long-term efficacy and their role in the treatment of high-risk patients. ABSTRACT: Despite significant improvements in the treatment of multiple myeloma (MM), it remains mostly incurable, highlighting a need for new therapeutic approaches. Patients with high-risk disease characteristics have a particularly poor prognosis and limited response to current frontline therapies. The recent development of immunotherapeutic strategies, particularly T cell-based agents have changed the treatment landscape for patients with relapsed and refractory disease. Adoptive cellular therapies include chimeric antigen receptor (CAR) T cells, which have emerged as a highly promising therapy, particularly for patients with refractory disease. Other adoptive cellular approaches currently in trials include T cell receptor-based therapy (TCR), and the expansion of CAR technology to natural killer (NK) cells. In this review we explore the emerging therapeutic field of adoptive cellular therapy for MM, with a particular focus on the clinical impact of these therapies for patients with high-risk myeloma.