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Multiple Myeloma (MM) management is rapidly evolving, with a spectrum of novel treatments that have changed our approach to the therapy. Proteasome inhibitors (PIs) have revolutionized the scenario of both relapsed/refractory and newly diagnosed patients. The efficacy of bortezomib, the first PI approved, followed by carfilzomib and, the oral ixazomib, have been tested in several trials as single agents or in combination. Areas covered: In this review, the authors summarize mechanism of action, efficacy and safety of proteasome inhibitors in MM and focus on data derived from clinical trials, analyzing adverse events and their relative management. Expert opinion: The authors believe that, currently, the best course of action in the treatment of MM is to use PIs in combination with immunomodulatory drugs (IMiDs) and/or with monoclonal antibodies for all patients. However, based on the patient-specific characteristics, it is important to avoid inappropriate discontinuation by knowing the single side effects of every agent in order to balance their efficacy and safety.

Multiple myeloma (MM) is the second-most common hematologic malignancy after diffuse large B-cell lymphoma. Despite the improvement in response and survival rates following the introduction of novel therapies, only a few patients are cured, and the majority of MM patients experience several relapses and receive multiple lines of treatment. Currently, bortezomib and lenalidomide are the core component of treatment both at the time of diagnosis and at the relapse as well as the new proteasome inhibitors (PIs), such as carfilzomib and ixazomib, and the next-generation immunomodulatory drug, pomalidomide, are now available for patients in relapse. In addition, drugs with a different mechanism of action, such as the histone deacetylase inhibitor and the monoclonal antibodies (MoAb) targeting SLAMF7 or CD38, are a part of the anti-myeloma armamentarium and are very important for heavily pretreated or double refractory to a PI and IMiD patients. In this paper, we focus on the efficacy as well as toxicities of CD38 antibodies used both as a single agent and in combination as multiple myeloma treatment.