It is well described that immune dysfunction is involved in the transformation of multiple myeloma (MM) from benign precursor states, smoldering myeloma, and monoclonal gammopathy of undetermined significance. The immune system in MM patients demonstrates progressive impairment with time. Mechanisms of immune impairment have been proposed to be involved in the fading tumor surveillance, production of immune-suppressive cytokines, suppression mediated by regulatory T-cells, myeloid-derived suppressor cells, tumor associated macrophages, and the expression of inhibitory immune checkpoints on cells present in the tumor microenvironment.

Emerging data suggests that attempts to revive and engage the innate and adaptive immune system can change the natural course of the disease. Efforts have been made to harness the immune response against multiple myeloma through the application of therapies such as IMiDS, monoclonal antibodies, autologous stem cell transplantation, chimeric antigen receptor T-cells, immune checkpoint blockades, bi-specifics antibodies, novel inhibitors, and epigenetic modulators. These immune/cancer cell therapies have led to tremendous advances in therapeutic options and prolonged the life expectancy of multiple myeloma patients. However, a subset of patients continues to be unresponsive, and nearly all patients succumb to their disease, thus emphasizing the need to further improve the therapeutic paradigm. Future work targeting immune defects in multiple myeloma is warranted to augment or restore T-cell or B-cell responses using the next generation of immune-modulating agents.

This Research Topic aims to address existing and novel strategies to advance combination immunotherapies in the preclinical and clinical settings of multiple myeloma and plasma cell dyscrasias. Particular attention will be given to hypothesis-driven studies with strong preliminary data and novel ideas to improve/enhance the long-lasting effects of these therapies.

We are interested in Original Research, Review/Mini Review, and Perspectives articles, focusing on but not limited to the following areas:

• Use of cellular therapies in MM and plasma cell dyscrasias
• Novel approaches to autologous or allogeneic transplantation
• Role of the microbiome as it correlates with treatment response
• Novel combinations with immune checkpoint inhibitors
• T- or B-cell exhaustion
• Changes in immune milieu with progression from smoldering to symptomatic myeloma
• Immune defects in multiple myeloma
• Bone marrow microenvironment
• Restoration of T-cell responses

In vitro and in vivo studies related to new immunotherapeutic approaches, clinical studies, population-based studies, novel target exploration, epigenetic insights, and biomarkers are of interest.

Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.

Dr. Noa Biran has research support from Karyopharm, Janssen, Amgen, and BMS and is on the speakers bureau of Pfizer, Janssen, and Sanofi. Dr. David Siegel receives honoraria and is on the speakers bureau of BMS, Karyopharm, Janssen Oncology, and GSK, receives honoraria from K36 Therapeutics and Sanofi, and is an equity holder in COTA. The other topic editors declare no competing interests with regard to the topic theme.

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