Ixazomib: an oral proteasome inhibitor for the treatment of multiplemyeloma

Introduction: Over the past decade, the introduction of proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs) has dramatically improved the progression-free and overall survival of patients with multiple myeloma (MM). Ixazomib, a second-generation oral reversible 20S PI, is one of the first oral PIs in development for patients with MM.Areas covered: The current literature examining the outcomes of MM patients treated with ixazomib. A literature search using PubMed and abstracts presented at international conferences was conducted to include relevant preclinical and prospective clinical trials using ixazomib in MM. Preclinical studies have demonstrated both independent and synergistic antitumor activity of ixazomib. Phase I and II studies have established safety and efficacy of ixazomib in once and twice weekly dosing in the upfront and relapsed/refractory disease in transplant and non-transplant eligible populations. Commonly seen adverse events include cytopenias, skin toxicities and gastrointestinal effects. Grade 3 peripheral neuropathy was not commonly observed. Phase 3 trials are ongoing, evaluating ixazomib, dexamethasone and lenalidomide for patients with newly diagnosed and relapsed/refractory MM.Expert opinion: It is likely that ixazomib will be a notable addition to the MM therapeutic armamentarium given the convenience of oral dosing, its relative tolerability, and efficacy.