Selinexor in patients with relapsed or refractory multiple myeloma

Although the survival rate of patients with multiple myeloma has significantly improved in the last years thanks to the introduction of various classes of new drugs, such as proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies, the vast majority of these subjects’ relapse with a more aggressive disease due to the acquisition of further genetic alterations that may cause resistance to current salvage therapies. The treatment of these often “triple” (or even more) refractory patients remains challenging, and alternative approaches are required to overcome the onset of that resistance. Immunotherapies with novel monoclonal, drug-conjugated, or bispecific antibodies, as well as the use of chimeric antigen receptor T cells, have been recently developed and are currently investigated. However, other non-immunologic therapeutic regimens based on melfluflen, venetoclax, or selinexor, three molecules with new mechanisms of action, have also shown promising results in the setting of relapsed/refractory myeloma. Selinexor is a first-inclass, oral, slowly reversible, highly specific inhibitor of exportin-1 (XPO-1) which is an important nuclear exporter for more than 200 proteins, including many tumor-suppressor proteins. In this review, we report the latest literature data on selinexor, with a particular focus on its efficacy and safety in multiple myeloma.