Does the Addition of Ixazomib to Lenalidomide and Dexamethasone Improve Survival in MM?

A study presented at the 2020 Society of Hematologic Oncology Annual Meeting found that the addition of ixazomib to lenalidomide and dexamethasone significantly extended progression-free survival (PFS; primary endpoint) in transplant-ineligible patients with newly diagnosed multiple myeloma (MM) with high-risk cytogenetics.

The randomized, phase III TOURMALINE-MM2 trial included 705 adults with newly diagnosed MM who were not eligible for autologous hematopoietic cell transplantation. Patients were randomized to receive lenalidomide 25 mg and dexamethasone 40 mg either with (n=351; median age, 73 years) or without (placebo group; n=354; median age, 74 years) ixazomib 4 mg. After 18 cycles, dexamethasone was discontinued, and patients received reduced doses of ixazomib and lenalidomide until disease progression or unacceptable toxicity.

Median follow-up was 55.3 months in the ixazomib group and 55.8 months in the placebo group. Median PFS was longer among ixazomib-treated patients than placebo (35.3 months vs. 21.8 months; hazard ratio [HR], 0.83), although this was not statistically significant.

Overall response rates were similar in the ixazomib and placebo groups (82% vs. 80%). However, a higher percentage of ixazomib-treated patients achieved complete response (26% vs. 14%; odds ratio [OR], 2.1; P<0.001) or very-good partial response or better (63% vs. 48%; OR, 1.87; P<0.001). Median time to progression was 45.8 months in the ixazomib group versus 26.8 months in the placebo group (HR, 0.736; P=0.008).

Longer median time to progression was observed in the ixazomib group (45.8 months vs. 26.8 months; HR, 0.73; P=0.008). Median overall survival did not differ significantly between the groups (57.8 months vs. 58.6 months, respectively; HR, 0.99).

Among a cohort of patients with high-risk cytogenetics (38% in ixazomib group and 41% in placebo group), there was a statistically significant PFS benefit in the ixazomib cohort (median, 23.8 months vs. 18.0 months; HR, 0.69; P=0.019).

More patients in the ixazomib-treated group experienced grade ≥3 treatment-related adverse events (AEs; 88% vs. 81%) and treatment-related AEs that resulted in treatment discontinuation (35% vs. 27%). Eight percent of patients in the ixazomib group died during the study compared with 6% of those in the placebo cohort.

“[Ixazomib plus lenalidomide and dexamethasone] is a feasible treatment option for certain transplant-ineligible patients who could benefit from an all-oral triplet combination,” the authors concluded.