Boosting Immunity against Multiple Myeloma

Abstract

Despite the improvement of patient's outcome obtained by the current use of immunomodulatory drugs, proteasome inhibitors or anti-CD38 monoclonal antibodies, multiple myeloma (MM) remains an incurable disease. More recently, the testing in clinical trials of novel drugs such as anti-BCMA CAR-T cells, antibody-drug conjugates or bispecific antibodies broadened the possibility of improving patients' survival. However, thus far, these treatment strategies have not been able to steadily eliminate all malignant cells, and the aim has been to induce a long-term complete response with minimal residual disease (MRD)-negative status. In this sense, approaches that target not only myeloma cells but also the surrounding microenvironment are promising strategies to achieve a sustained MRD negativity with prolonged survival. This review provides an overview of current and future strategies used for immunomodulation of MM focusing on the impact on bone marrow (BM) immunome.

Keywords: bone marrow immune microenvironment; immunotherapy; multiple myeloma.

Figure 1

Overview of different immunotherapeutic approaches targeting the suppressive MM BM immune microenvironment and boosting innate and/or adaptive anti-tumor responses. NK, natural killer; M-MDSCs, monocytic MDSCs; PMN-MDSCs, polymorphonuclear myeloid-derived suppressor cells; Bregs, regulatory B cells; Tregs, regulatory T cells; pDCs, plasmacytoid dendritic cells; mDCs, myeloid DCs); IMIDs, Immunomodulators; mAbs, monoclonal antibodies; ADCs, antibody–drug conjugates; ICIs, immune checkpoint inhibitors; SCT, stem cell transplantation; CAR, chimeric antigen receptor; MILs, marrow-infiltrating lymphocytes; TCR, T cell receptor. Activation and suppression of immune populations showed by a line and stop line, respectively. Immunotherapies that are under development for MM are listed in grey.