Treatment Strategy for Multiple Myeloma to Improve Immunological Environment and Maintain MRD Negativity.

Kazuhito Suzuki,Shingo Yano,Kaichi Nishiwaki

doi:10.3390/cancers13194867

Kazuhito Suzuki, Shingo Yano + Show 1 more

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https://doi.org/10.3390/cancers13194867

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Abstract

Simple SummaryImproving the immunological environment and eradicating minimal residual disease (MRD) are the two main treatment goals for long-term survival in patients with multiple myeloma (MM). An improved immunological environment may be useful for maintaining MRD negativity. Whether the ongoing treatment should be continued or changed if the MRD status remains positive is controversial. In this case, genetic, immunophenotypic, and clinical analysis of residual myeloma cells may be necessary to select the effective treatment for the residual myeloma cells. The purpose of this review is to discuss the MM treatment strategy to “cure MM” based on currently available therapies and expected immunotherapies via improvement of the immunological environment and maintenance of MRD negativity.Improving the immunological environment and eradicating minimal residual disease (MRD) are the two main treatment goals for long-term survival in patients with multiple myeloma (MM). Immunomodulatory drugs (IMiDs), monoclonal antibody drugs (MoAbs), and autologous grafts for autologous stem cell transplantation (ASCT) can improve the immunological microenvironment. ASCT, MoAbs, and proteasome inhibitors (PIs) may be important for the achievement of MRD negativity. An improved immunological environment may be useful for maintaining MRD negativity, although the specific treatment for persistent MRD negativity is unknown. However, whether the ongoing treatment should be continued or changed if the MRD status remains positive is controversial. In this case, genetic, immunophenotypic, and clinical analysis of residual myeloma cells may be necessary to select the effective treatment for the residual myeloma cells. The purpose of this review is to discuss the MM treatment strategy to “cure MM” based on currently available therapies, including IMiDs, PIs, MoAbs, and ASCT, and expected immunotherapies, such as chimeric antigen receptor T cell (CAR-T) therapy, via improvement of the immunological environment and maintenance of MRD negativity.

Highlights

The purpose of this review is to describe the importance of improving the immune environment in MM patients and its therapeutic strategies, the clinical significance of minimal residual disease (MRD)
We describe the treatment of residual myeloma cells in MRD-positive patients and the future MRD status-adapted treatment strategies
We previously reported that the total therapy approach combining these four treatment approaches could be essential, considering the bone marrow (BM) microenvironment, such as adhesion to bone marrow stromal cells (BMSCs), vascular niche, and endosteal niche [171]

Summary

Introduction

Multiple myeloma (MM) is a hematopoietic malignancy of the plasma cells, and the survival of patients with MM has been prolonged by the development of new agents in the last few decades, it is still an incurable disease [1,2]. To cure MM, it is important to improve the immune environment and ensure persistent minimal residual disease (MRD) negativity [3,4,5]. An improved immune environment leads to the long-term survival of patients with myeloma due to enhanced immunological potency against myeloma cells [6]. The clinical development of an immune checkpoint inhibitor for myeloma, which has played an important role in the treatment of solid malignant tumors, is under way [12]. Autologous grafts used in autologous stem cell transplantation (ASCT), which is still the standard treatment for patients with MM [13,14], have been reported to improve the immune environment [15]

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