Ixazomib is an oral proteasome inhibitor recently approved by the US Food and Drug Administration for the treatment of relapsed multiple myeloma (MM). In the dose-escalation studies, ixazomib was tolerated up to a dose of 5.5 mg given every week as a single agent, while a dose of 4 mg was utilized in the combination studies with lenalidomide. In this randomized phase 2 study, patients were given ixazomib 4 mg (arm A) or 5.5 mg weekly (arm B) for 3 weeks with a week off along with weekly dexamethasone (40 mg) in patients with relapsed MM. The primary objective was to determine the confirmed overall response rate; secondary objectives included progression-free survival and overall survival. A total of 71 patients were included in the study population; 1 patient was ineligible.
Baseline characteristics were similar in the 2 arms. Participants’ median age was 70 years; 53% were male. The median number of prior therapies was 4 (range, 2-6); 90% of the patients had received prior immunomodulatory drugs, 71% had prior transplant, and 31% had prior bortezomib. At follow-up, 19 (54%) and 22 (63%) patients had disease progression in arms A and B, respectively, and 19 (29%) patients remained on treatment—10 in arm A (29%) and 9 (26%) in arm B. A total of 11 (31%) patients in arm A and 18 (51%) patients in arm B achieved an overall response to treatment. Median event-free survival rates were 8.4 months in arm A and 6.9 months in arm B. Median duration of response was also statistically similar; 16.7 months in arm A and 16.3 months in arm B.
Overall, treatment was well tolerated with 2 patients in arm A and 3 patients in arm B discontinuing treatment for adverse events (AEs). The most common toxicities were fatigue, thrombocytopenia, diarrhea, and nausea, with more grade 3 toxicities among patients in arm B.
Researchers concluded that ixazomib in combination with dexamethasone showed significant antimyeloma activity, relatively deep responses, and primarily manageable toxicities in this group of patients with relapsed MM. The higher dose of ixazomib appears to be associated with a higher response rate as well as a higher rate of AEs requiring dose reductions.