TOURMALINE-MM2: Oral Ixazomib Combo for Transplant-Ineligible Multiple Myeloma

A study published in Blood evaluated outcomes of oral ixazomib with lenalidomide plus dexamethasone for the treatment of patients with newly diagnosed, transplant-ineligible multiple myeloma (MM).

The TOURMALINE-MM2 trial was a double-blind, placebo-controlled study of 706 patients with newly diagnosed, transplant-ineligible MM. Participants were randomized to a regimen of lenalidomide plus dexamethasone with or without ixazomib 4 mg. Overall, 351 patients received the ixazomib combination and 354 received a placebo. After 18 cycles, dexamethasone use was discontinued. The experimental cohort then received continued treatment with reduced dose ixazomib plus lenalidomide (3 mg and 10 mg, respectively) until disease progression or unacceptable toxicity. The study’s primary endpoint was progression free survival (PFS).

The addition of ixazomib spurred a non-statistically significant increase in PFS. The median PFS for the experimental group was 35.3 months, compared with 21.8 months in the placebo group (hazard ratio [HR] 0.83; 95% confidence interval [CI] 0.676-1.018; P = 0.73). In the ixazomib group, 26% of patients achieved a complete response and 63% achieved a very good partial response or better, compared with 14% and 48% of the placebo group, respectively (P < 0.001). Among patients with high-risk MM, median PFS was 23.8 months for ixazomib versus 18.0 months for the placebo (HR 0.69; P = 0.019).

Grade 3 or higher treatment-related adverse events (AEs) occurred in 88% and 81% of patients in the experimental versus control groups. Mortality on study occurred in 8% of patients in the ixazomib group and 6% of patients in the placebo group.

In conclusion, the researchers wrote, “TOURMALINE-MM2 demonstrates that ixazomib [with lenalidomide plus dexamethasone] is a feasible treatment option for certain transplant-ineligible patients with newly diagnosed MM who could benefit from an all-oral triplet regimen.”