Background Maintenance therapy following autologous stem cell transplantation can delay disease progression and prolong survival in multiple myeloma (MM). Ixazomib is ideally suited for maintenance therapy given its efficacy, convenient once-weekly oral dosing, and low toxicity profile. Methods The phase 3, double-blind, placebo-controlled, TOURMALINE-MM3 study randomised 656 patients with newly diagnosed MM from 227 clinical/hospital sites in 30 countries in Europe, the Middle East, Africa,

Although lenalidomide-based combinations, such as lenalidomide plus a proteasome inhibitor or an anti-CD38 monoclonal antibody, improve the overall response rate, progression-free survival, and overall survival of patients with relapsed/refractory multiple myeloma (RRMM), there is a tendency to use these regimens as a frontline treatment. This strategy has led to the development of refractoriness early in the disease course, usually after the patient’s first treatment. Since lenalidomide-free regimens have so far shown limited efficacy in lenalidomide-refractory patients, there is an unmet need for other treatment options. In this review, we discuss the therapeutic options available to treat the general population of lenalidomide-refractory patients (mono, double and triple refractory) and the subpopulation of patients with other high-risk features such as renal failure, extramedullary disease, and high-risk cytogenetics. Moreover, new promising individual therapies and the possible impact of immunotherapy in RRMM patients are debated.

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