Boosting Immunity against Multiple Myeloma

SIMPLE SUMMARY: Multiple myeloma is a hematological malignancy arising from the proliferation of tumor antibody-producing cells in the bone marrow. In this cancer, tumor growth is facilitated by a permissive bone marrow microenvironment including dysfunctional immune cells that lose their ability to control cancer cells and become “toxic friends”. Immunotherapy is a form of cancer treatment that aims to stimulate the immune system to “fight back” tumor cells. Several immunotherapies have been approved for clinical use and many others are currently under clinical trials. In this review, we focus on current and future immunotherapies used in multiple myeloma with impact on bone marrow immune microenvironment cells, also known as the bone marrow immunome. 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.