Can Ixazomib Improve Survival for Newly Diagnosed Patients with Multiple Myeloma?

The international, multicenter, double-blind, placebo-controlled, phase III TOURMALINE-MM4 trial found that post-induction maintenance ixazomib in non–transplant-eligible newly diagnosed patients with multiple myeloma (MM) improved progression-free survival (PFS) compared with placebo. In a subgroup analysis presented at the 2020 ASH Annual Meeting, ixazomib improved PFS compared with placebo regardless of patient age or frailty status.

Patients who achieved a partial response (PR) or better after six to 12 months of standard induction therapy were randomized 3:2 to receive ixazomib (n=425) or placebo (n=281) maintenance therapy for up to 24 months. Patients were classified as fit, unfit, or frail based on the sum of four components: age (<75 vs. 75-80 years vs. >80 years), the Katz Index of Independence in Activities of Daily Living (ADL; >4 vs. ≤4), the Lawton Instrumental ADL Scale (>5 vs. ≤5), and the Charlson Comorbidity Index (≤1 vs. ≥2).

Across frailty groups, researchers observed:

  • A higher rate of complete response (CR) or very-good PR (VGPR) in fit patients.
  • A lower rate of International Staging System (ISS) stage III disease in unfit patients.
  • A higher rate of ISS stage III disease and a lower rate of CR or VGPR in frail patients.

PFS benefit with ixazomib, compared with placebo, was observed across age groups:

  • Patients aged <65 years: hazard ratio (HR), 0.576 (95% confidence interval [CI], 0.299-1.108; P=0.095; median, 11.0 vs. 9.3 months).
  • Patients aged 65 to 74 years: HR, 0.615 (95% CI, 0.467-0.810; P<0.001; median, 17.9 vs. 9.3 months).
  • Patients aged ≥75 years: HR, 0.740 (95% CI, 0.537-1.019; P=0.064; median, 16.7 vs. 10.2 months).

Across age and frailty groups, grade ≥3 treatment-related adverse events (AEs), serious AEs, and treatment discontinuation due to AEs were higher or similar with ixazomib versus placebo. AE rates were generally higher in older age and unfit/frail patients in both treatment cohorts.

“Ixazomib is a feasible and effective maintenance option for prolonging PFS across this heterogeneous patient population,” the researchers concluded.


Bringhen S, Pour L, Benjamin R, et al. Progression-Free Survival (PFS) Benefit Demonstrated and Quality of Life (QoL) Maintained across Age and Frailty Subgroups with the Oral Proteasome Inhibitor (PI) Ixazomib Vs Placebo As Post-Induction Maintenance Therapy in Non-Transplant Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts): Analysis of the TOURMALINE-MM4 Phase 3 Trial. Abstract 1381. Presented at the 62nd American Society of Hematology Annual Meeting & Exposition, Dec. 2-11, 2020.