Proteasome inhibitors have become an integral part of myeloma therapy. 
Considerable efforts have gone into optimizing this therapeutic approach to 
obtain maximal proteasome inhibition with least toxicity. Ixazomib is the first 
oral proteasome inhibitor to enter the clinic and has been studied as a single 
agent as well as in various combinations. The current trial was designed to 
examine the efficacy and toxicity of combining 2 different doses of ixazomib (4 
mg and 5.5 mg given weekly for 3 of 4 weeks) with 40 mg weekly of dexamethasone, 
in relapsed myeloma. Seventy patients were enrolled, 35 patients randomly 
assigned to each ixazomib dose. Overall, 30 (43%; 95% confidence interval, 
31-55) of the patients achieved a confirmed partial response or better, with 31% 
achieving a response with 4 mg and 54% with 5.5 mg of ixazomib. The median 
event-free survival (EFS) for the entire study population was 8.4 months; 1-year 
overall survival was 96%. The EFS was 5.7 months for patients with prior 
bortezomib exposure and 11.0 months for bortezomib-naïve patients. A grade 3 or 
4 adverse event considered at least possibly related to treatment was seen in 11 
(32%) patients at 4 mg and in 21 (60%) at 5.5 mg. Dose reductions were more 
frequent with 5.5 mg dose. Overall, the ixazomib with dexamethasone has good 
efficacy in relapsed myeloma, is well-tolerated and with higher response rate at 
5.5 mg, albeit with more toxicity. This study was registered at 
www.clinicaltrials.gov as #NCT01415882.