The addition of ixazomib to lenalidomide and dexamethasone significantly prolonged progression-free survival compared lenalidomide plus dexamethasone alone in patients with relapsed and/or refractory multiple myeloma, a study published in The New England Journal of Medicine has shown.1
Ixazomib is the first oral proteasome inhibitor approved by the U.S. Food and Drug Administration in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least 1 prior therapy. Approval was based on the results of the phase 3 TOURMALINE-MM1 trial.
For the double-blind, placebo-controlled study, researchers enrolled 722 patients with relapsed and/or refractory multiple myeloma and randomly assigned them 1:1 to receive lenalidomide plus dexamethasone with either ixazomib or placebo.
Results showed that at a median follow-up of 14.7 months, median progression-free survival was 20.6 months with ixazomib compared with 14.7 months with placebo (HR, 0.74; P=.01). Subgroup analyses demonstrated a progression-free survival benefit with the ixazomib regimen in all prespecified patient subgroups, including in patients with high-risk cytogenetic abnormalities.
Researchers found that the overall response rate was 78% in the ixazomib arm and 72% in the placebo arm; the rate of complete response or very good partial response was 48% and 39%, respectively. The median time to response was 1.1 months with ixazomib vs 1.9 months with placebo. Median duration of response was 20.5 months and 15.0 months, respectively. Median overall survival has not yet been reached.
In terms of safety, serious adverse events were reported with 47% of patients who received ixazomib and 49% of those who had placebo. Grade 3 or worse adverse events were reported in 74% and 69% of patients in the ixazomib arm and placebo arm, respectively. Grade 3 or 4 thrombocytopenia was more frequently reported in the ixazomib group, as were rash and gastrointestinal adverse events. The incidence of peripheral neuropathy was 27% in the ixazomib group and 22% in the placebo group.
Of note, patient-reported quality of life was similar between the 2 treatment arms.
RELATED: Updated 2016 NCCN Guidelines in Oncology for Multiple Myeloma Highlight Significant Changes in Clinical Practice
“The TOURMALINE-MM1 results demonstrated that ixazomib in combination with lenalidomide and dexamethasone is an effective and tolerable oral regimen with a manageable safety profile for patients with relapsed and/or refractory multiple myeloma,” said lead investigator Philippe Moreau, MD, of the University of Nantes in France.2
Preliminary findings from TOURMALINE-MM1 were previously presented at the American Society of Hematology (ASH) 57th Annual Meeting.
- Moreau P, Masszi T, Grzasko N, et al. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;374:1621-1634.
- Phase 3 trial results for first oral proteasome inhibitor Ninlaro (ixazomib) published in The New England Journal of Medicine [news release]. Cambridge, MA: Takeda Oncology; April 27, 2016. http://investor.millennium.com/phoenix.zhtml?c=80159&p=irol-newsArticle&ID=2162391. Accessed April 27, 2016.