Adding ixazomib to the combination of lenalidomide/dexamethasone resulted in a more than 35% improvement in the risk for disease progression or death in patients with relapsed or refractory multiple myeloma.
Use of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide/dexamethasone resulted in a more than 35% improvement in the risk for disease progression or death in patients with relapsed or refractory multiple myeloma compared with lenalidomide/dexamethasone alone, according to the results of the phase III trial TOURNALINE-MM1 trial published in the New England Journal of Medicine.
Patients assigned to ixazomib had a median progression-free survival that was about 6 months longer than patients assigned to lenalidomide/dexamethasone alone.
In addition, “data on median progression-free survival suggest that an ixazomib regimen may improve the prognosis for patients with high-risk cytogenetic features, which have traditionally been associated with a poor prognosis, by lengthening the progression-free survival to a point that is similar to that among patients with standard-risk cytogenetic features,” according to researcher Philippe Moreau, MD, of the University Hospital HÃ´tel Dieu, Nantes, Frances, and colleagues.
These data served as the basis for the US Food and Drug Administration approval of ixazomib in November 2015.
In the TOURNALINE-MM1 trial, Moreau and colleagues randomly assigned 722 patients with relapsed, refractory, or relapsed and refractory multiple myeloma to ixazomib plus lenalidomide/dexamethasone or placebo plus lenalidomide/dexamethasone. Nineteen percent of patients had high-risk cytogenetic abnormalities.
After a median follow-up of 14.7 months, patients assigned ixazomib had a median progression-free survival of 20.6 months compared with 14.7 months for patients assigned placebo (hazard ratio [HR], 0.74; 95% CI, 0.59-0.94; P = .01). Median overall survival has not been reached in either study group.
“The benefit of the ixazomib regimen with respect to progression-free survival was observed consistently in all key prespecified subgroups, including in the subgroups of patients with a poor prognosis, such as elderly patients, those who have received two or three prior therapies, those with advanced-stage disease, and those with high-risk cytogenetic abnormalities, for whom lenalidomide–dexamethasone has been shown to be a less effective treatment on the basis of emerging data,” the researchers wrote.
The median progression-free survival among patients with high-risk abnormalities was 21.4 months compared with 9.7 months among patients assigned placebo (HR, 0.54 [95% CI, 0.32-0.92]; P = .02). Specifically, among the 10% of patients with del(17p), in those assigned ixazomib the median progression-free survival was 21.4 months compared with 9.7 months for the placebo group (HR, 0.60 [95% CI, 0.29–1.24]).
The overall response rate was 78.3% in the ixazomib group and 71.5% in the placebo group (P = .04). According to the researchers, responses were “rapid and durable and deepened with increasing duration of treatment.”
Rates of serious adverse events and death during the study period were similar between the two study arms. However, grade 3/4 thrombocytopenia occurred more frequently in patients assigned ixazomib, as did rash and gastrointestinal adverse events.
“In consideration of its adverse-event profile and efficacy, this all-oral regimen provides an additional therapeutic option for patients with relapsed, refractory, or relapsed and refractory multiple myeloma,” the researchers concluded.
This study was funded by Millennium Pharmaceuticals.