In a phase 3 clinical trial involving patients with relapsed, treatment-resistant multiple myeloma, a combination of the oral drugs ixazomib, lenalidomide, and dexamethasone kept the disease in check significantly longer than lenalidomide and dexamethasone alone, investigators at Dana-Farber Cancer Institute and other research centers report in the New England Journal of Medicine.
The study found the all oral three-drug combination extended progression-free survival by 40 percent over that achieved by lenalidomide and dexamethasone alone, with no major difference in side effects and favorable tolerability, as well as an overall improvement in quality of life. Progression-free survival measures the length of time after treatment in which the disease does not get worse. At a median follow-up of 14.7 months, patients in the ixazomib group had a median progression-free survival of 20.6 months, vs. 14.7 months for patients in the lenalidomide and dexamethasone-only group.
In addition, the combination was especially active in high risk patients, who were defined as those with adverse cytogenetics predictive of poor outcome in their tumor.
The trial enrolled a total of 722 patients with relapsed, refractory, or relapsed and refractory multiple myeloma, who were randomly assigned to receive either the two-drug or three-drug combination.
Ixazomib (Ninlaro®) is a proteasome inhibitor that blocks the ability of cancer cells to reuse certain proteins. It was approved last year by the U.S. Food and Drug Administration for patients with multiple myeloma who have received at least one previous therapy.
In the trial, patients receiving the triple-drug combination responded to treatment in a median of 1.1 months, compared to 1.9 months for those receiving the two-drug combination. The three-drug combination was also associated with a longer median duration of response – 20.5 months vs. 15.0 months.
The rates of serious adverse effects were similar in the two study groups: 47 percent in the ixazobmib group and 49 percent in the two-drug group.
“This first all oral combination approach of a proteasome inhibitor with an immuno-modulatory agent and low dose dexamethasone represents another important step forward in improving outcome, and further validates the synergy of this triplet therapy, whilst at the same time providing a better tolerated and more convenient treatment approach for our patients,” said study senior author and co-principal investigator, Paul Richardson, MD, clinical program leader and director of clinical research at the Dana-Farber’s Jerome Lipper Center for Multiple Myeloma, and RJ Corman Professor of Medicine at Harvard Medical School.