Multiple Myeloma Therapy: Emerging Trends and Challenges

SIMPLE SUMMARY: Multiple myeloma (MM) is a frequent hematological malignancy characterized by the uncontrolled growth of clonal plasma cells, primarily in the bone marrow. Over the past years, novel therapies have been discovered and introduced into clinical practice that have dramatically changed the treatment landscape of MM. Despite the tremendous advances, MM remains incurable, with poor outcomes particularly in patients with relapsed/refractory disease, emphasizing the need for new therapeutic approaches. In this review we discuss the current treatment paradigm of multiple myeloma and focus on promising future approaches. ABSTRACT: Multiple myeloma (MM) is a complex hematologic malignancy characterized by the uncontrolled proliferation of clonal plasma cells in the bone marrow that secrete large amounts of immunoglobulins and other non-functional proteins. Despite decades of progress and several landmark therapeutic advancements, MM remains incurable in most cases. Standard of care frontline therapies have limited durable efficacy, with the majority of patients eventually relapsing, either early or later. Induced drug resistance via up-modulations of signaling cascades that circumvent the effect of drugs and the emergence of genetically heterogeneous sub-clones are the major causes of the relapsed-refractory state of MM. Cytopenias from cumulative treatment toxicity and disease refractoriness limit therapeutic options, hence creating an urgent need for innovative approaches effective against highly heterogeneous myeloma cell populations. Here, we present a comprehensive overview of the current and future treatment paradigm of MM, and highlight the gaps in therapeutic translations of recent advances in targeted therapy and immunotherapy. We also discuss the therapeutic potential of emerging preclinical research in multiple myeloma.