Proteasome inhibitors in first-line treatment of transplant-ineligible multiple myeloma patients.

Since the turn of the century, many agents against multiple myeloma (MM) have been introduced into daily clinical practice. The development of further agents is ongoing and some of these will reach the point of use in clinical practice in the near future. As various treatment options become available, the selection of an appropriate treatment strategy for an individual patient becomes more important. Treatment selection and decision making are based on the following two apparently opposite factors: 1) generalized findings and evidence from clinical trials, and 2) disease risks and background of individuals, which are diverse among patients. Proteasome inhibitors (PIs) are central players in MM treatment. In this review, we summarize evidence for the efficacy and safety of a first generation PI, bortezomib, and discuss its advantages in controlling disease risks and myeloma-defining events in patients with transplant-ineligible, untreated, newly diagnosed MM (NDMM). We also highlight on recent knowledge regarding the use of second generation PIs such as carfilzomib and ixazomib in the treatment of transplant-ineligible, untreated NDMM.