INTRODUCTION: Proteasome inhibition is a mainstay in the treatment of multiple 
myeloma (MM). Bortezomib, the first proteasome inhibitor (PI) approved for MM 
therapy, has shown efficacy in relapsed/refractory patients and in the 
front-line setting. Among second-generation PIs, MLN9708 ( ixazomib ) is the 
first oral compound to be evaluated in MM treatment and has shown improvement in 
pharmacokinetic and pharmacodynamic parameters compared with bortezomib with a 
similar efficacy in the control of myeloma growth and in the prevention of bone 
loss.
AREAS COVERED: In this review, the authors discuss the rationale for use of PIs. 
They then summarize the clinical development of ixazomib in MM, from initial 
Phase I to Phase II studies as a monotherapy and in combination with other 
chemotherapeutics.
EXPERT OPINION: Preliminary data of Phase I/II trials showed that ixazomib had a 
good safety profile and exerted anti-myeloma activity as a single agent in 
relapsed/refractory patients. Furthermore, ixazomib also had efficacy in 
patients who were refractory to bortezomib. Its use in combination with 
lenalidomide and dexamethasone was shown to be an effective and well-tolerated 
regimen in up-front treatment leading to minimal residual disease negativity in 
a significant number of patients. Results of Phase III trials, evaluating 
ixazomib in induction or maintenance therapy, are awaited.