The oral proteasome inhibitor ixazomib, when added to lenalidomide/dexamethasone, significantly increased progression-free survival in patients with multiple myeloma compared with placebo, a randomized phase 3 study reported in the New England Journal of Medicine.1
At a median follow-up of 14.7 months, median progression-free survival—the study’s primary end point—was 20.6 months in the group that received ixazomib vs 14.7 months for placebo (hazard ratio [HR], 0.74; P = .01). This benefit was observed “in all prespecified patient subgroups, including in patients with high-risk cytogenetic abnormalities,” Philippe Moreau, MD, of the University Hospital Hôtel Dieu in France, and colleagues noted.
These results led the U.S. Food and Drug Administration to approve ixazomib in November 2015. The triple regimen is the first all-oral combination for multiple myeloma in the relapsed/refractory setting.
In the TOURMALINE-MM1 study, investigators randomly assigned 722 patients with relapsed, refractory, or relapsed and refractory multiple myeloma to receive lenalidomide/dexamethasone with ixazomib 4 mg (360 patients) or matching placebo (362 patients) on days 1, 8, and 15 in 28-day cycles.
The majority of patients (77%) had relapsed disease. High-risk cytogenetic abnormalities were detected in the 76% of patients for whom cytogenetic analysis results were available; this included 10% with del(17p).
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Median age was 66 years (range, 30 – 91 years), with 52% being older than 65 years; 57% were male, and 85% were white. A total of 61% of patients had received 1 prior therapy, 29% had received 2, and 10% had received 3. Of the group, 70% had received prior proteasome inhibitor therapy with bortezomib (69%) or carfilzomib (1%), 2% of whom had disease that was refractory to this class of agents, and 57% had undergone prior stem cell transplantation.