Even though the prognosis of patients with multiple myeloma is continuing to improve, all patients eventually develop relapsed refractory disease. Several novel therapeutics have been developed in the last few years including the second-generation proteasome inhibitor carfilzomib which has been approved for patients with relapsed and refractory multiple myeloma in the United States since 2012. Recently data from several phase III studies have become available showing the promising efficacy of carfilzomib in combination with lenalidomide, which led to the renewed approval of carfilzomib in combination with lenalidomide and dexamethasone for relapsed myeloma in 2015. Furthermore carfilzomib showed superiority over bortezomib on both efficacy and toxicity profiles, especially a profoundly lower incidence in polyneuropathy. Carfilzomib has been shown to partially overcome the negative effects of high-risk cytogenetics. Promising combinations of carfilzomib with histone deacetylase (HDAC) inhibitors, pomalidomide and several other novel therapeutics have been presented in early studies. The optimal dosing regimen and sequence of treatment regimens remain important questions for the future.
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