Article : Oral Triplet Therapy for Relapsed or Refractory Myeloma

Michael E. Williams, MD, ScM reviewing Moreau P et al. N Engl J Med 2016 Apr 28

Adding the oral proteasome inhibitor ixazomib to lenalidomide plus dexamethasone improved outcomes, even in high-risk subgroups.

Triplet therapy with an immunomodulatory drug, a proteasome inhibitor, and dexamethasone has improved response and progression-free survival in patients with multiple myeloma.

To test the activity of the oral proteasome inhibitor ixazomib in myeloma triplet therapy, investigators conducted an industry-sponsored, multicenter, randomized, double-blind, placebo-controlled phase III trial comparing lenalidomide plus dexamethasone with either ixazomib or placebo in 772 patients with relapsed or refractory disease.

At a median follow-up of 14.7 months, progression-free survival (the primary endpoint) was significantly longer with the ixazomib-containing triplet regimen versus the placebo regimen (20.6 vs. 14.7 months; P=0.01), although overall response rates were similar (78% and 72%, respectively). Responses in the ixazomib arm occurred early in treatment and improved over time. Of note, improved outcomes with ixazomib triplet therapy were observed among all prespecified high-risk patient subgroups, including those with poor-risk cytogenetics, age >75 years, stage III disease, and disease progression after two or three prior lines of therapy. Thrombocytopenia, rash, and gastrointestinal adverse effects, but not peripheral neuropathy, were more common among patients who received ixazomib.


Moreau P et al. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med 2016 Apr 28; 374:1621.