Ixazomib in the treatment of relapsed multiple myeloma

Abstract

Ixazomib (NINLARO, Takeda Pharmaceutical Company Limited) is the first oral proteasome inhibitor which approved in combination with lenalidomide and dexamethasone (IRd) for the treatment of patients with multiple myeloma who have received at least one prior therapy. Ixazomib is a boron-containing selective and reversible proteasome inhibitor that have high antitumor activity with excellent safety. This combination was approved based on the results from the phase 3, double-blind, placebo-controlled TOURMALINE-MM1 study, which demonstrated a 35% improvement in progression-free survival (PFS) for IRd versus placebo-Rd: median: 20.6 vs 14.7 months; hazard ratio (HR): 0.74, P = 0.012. PFS was improved in both high-and standard-risk cytogenetics subgroups with median PFS in high-risk patients 21.4 vs 9.7 months (HR 0.54; P = 0.021) and in standard-risk patients 20.6 vs15.6 months (HR 0.64; P = 0.007). The addition of ixazomib to Rd regimen was associated with minimal additional toxicity. Common grade ≥3 adverse events with ixazomib include gastrointestinal adverse events, rash, and thrombocytopenia. No significant inhibition of neuronal cell survival protease HtrA2/Omi was noted in response on ixazomib treatment in vitro that explains its minimal clinical peripheral neuropathy. The present review addresses the current knowledge regarding the clinical use of ixazomib in relapsed myeloma patient and the prospects for further expansion of therapeutic indications.