A phase 3 trial recently demonstrated that for transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM), the addition of the proteasome inhibitor ixazomib to treatment with lenalidomide plus dexamethasone (Rd) was feasible and showed efficacy. Results of the trial were reported in the journal Blood.
The placebo-controlled TOURMALINE-MM2 trial (ClinicalTrials.gov Identifier: NCT01850524) took place across 157 sites in multiple countries. In this trial, patients with NDMM were randomly assigned to receive either 4-mg oral ixazomib with Rd (351 patients) or a placebo with Rd (354 patients). Ixazomib or placebo was given on days 1, 8, and 15, lenalidomide was given on days 1 through 21, and dexamethasone was given on days 1, 8, 15, and 22 of 28-day cycles. Dexamethasone was discontinued after cycle 18 while lenalidomide treatment continued, and the ixazomib dosage was reduced to 3 mg among patients receiving it. Treatment continued until disease progression or unacceptable toxicity. Progression-free survival (PFS) was the primary study endpoint.
The median follow-up for PFS evaluation was 53.3 months for the ixazomib-Rd group and 55.8 months for the placebo-Rd group. The median PFS was 35.3 months with ixazomib-Rd, compared with 21.8 months for the placebo-Rd group, based on independent review. However, the longer PFS with ixazomib-Rd did not reflect a statistically significant difference (hazard ratio [HR], 0.830 [95% CI, 0.676-1.018]; P =.073).
For patients with high-risk cytogenetics, median PFS differed between treatments; median PFS was 23.8 months with ixazomib-Rd in these patients, and it was 18.0 months with placebo-Rd (HR, 0.690 [95% CI, 0.506-0.941]; P =.019).
In this study, the complete response rate was 25.6% with ixazomib-Rd, compared with 14.1% with placebo-Rd (odds ratio [OR], 2.10; P <.001). The rates of very good partial response or better were 63.0% with ixazomib-Rd and 47.7% with placebo-Rd (OR, 1.87; P <.001). Overall response rates were similar between groups (82.1% and 79.7%, respectively; P =.436).
Treatment-emergent adverse events (TEAEs) were primarily low grade, and grade ≥3 TEAEs were reported in 88.1% of patients from the ixazomib-Rd group and 81.4% of patients from the placebo-Rd group. Serious TEAEs were reported in 65.8% receiving ixazomib-Rd and 62.5% receiving placebo-Rd. Fatalities occurred in 7.6% of patients in the ixazomib-Rd group and 6.3% in the placebo-Rd group.
The study investigators considered ixazomib-Rd to show a clinically meaningful PFS benefit, even if not statistically significant. “TOURMALINE-MM2 demonstrates that ixazomib-Rd is a feasible treatment option for certain transplant-ineligible patients with NDMM who could benefit from an all-oral triplet regimen,” the researchers concluded in their report.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Facon T, Venner CP, Bahlis NJ, et al. Oral ixazomib, lenalidomide, and dexamethasone for newly diagnosed transplant-ineligible multiple myeloma patients. Blood. Published online March 24, 2021. doi:10.1182/blood.2020008787