Ixazomib Versus Placebo as Postinduction Maintenance Therapy in Newly Diagnosed Multiple Myeloma Patients: An Analysis by Age and Frailty Status of the TOURMALINE-MM4 Study

This TOURMALINE-MM4 secondary analysis was performed to determine if the progression-free survival (PFS) benefit observed in newly-diagnosed multiple myeloma (NDMM) patients with maintenance ixazomib versus placebo was driven by a particular subgroup of patients. PFS benefit with ixazomib versus placebo was seen across all age and frailty status subgroups. Ixazomib prolonged PFS across the heterogeneous population of NDMM patients. Background: The TOURMALINE-MM4 trial demonstrated a significant and clinically meaningful progression-free survival (PFS) benefit with ixazomib versus placebo as postinduction maintenance in nontransplant, newly-diagnosed multiple myeloma patients, with a manageable and well-tolerated toxicity profile. Materials and Methods: In this subgroup analysis, efficacy and safety were assessed by age ( < 65, 65-74, and = 75 years) and frailty status (fit, intermediate-fit, and frail). Results: In this analysis, PFS benefit with ixazomib versus placebo was seen across age subgroups, including patients aged < 65 years (hazard ratio [HR], 0.576; 95% confidence interval [CI], 0.299-1.108; P =.095), 65-74 years (HR, 0.615; 95% CI, 0.467-0.810; P <.001), and = 75 years (HR, 0.740; 95% CI, 0.537-1.019; P =.064). PFS benefit was also seen across frailty subgroups, including fit (HR, 0.530; 95% CI, 0.387-0.727; P <.001), intermediate-fit (HR, 0.746; 95% CI, 0.526-1.058; P =.098), and frail (HR, 0.733; 95% CI, 0.481-1.117; P =.147) patients. With ixazomib versus placebo, rates of grade = 3 treatment-emergent adverse events (TEAEs; 28-44% vs. 10-36%), serious TEAEs (15-29% vs. 3-29%), and discontinuation due to TEAEs (7-19% vs. 5-11%) were higher or similar across age and frailty subgroups, and generally somewhat higher in older age groups and intermediate-fit/frail patients in both arms. Treatment with ixazomib versus placebo did not adversely affect patient-reported quality-of-life scores across age and frailty status subgroups. Conclusion: Ixazomib is a feasible and effective maintenance option for prolonging PFS across this heterogeneous patient population.

Automated summary

This secondary analysis aimed to determine whether the PFS benefits observed in NDMM patients with maintenance ixazomib versus placebo were driven by a specific subgroup. The results showed that ixazomib prolonged PFS across all age and frailty status subgroups. It is concluded that ixazomib is a feasible and effective option for prolonging PFS in this heterogeneous patient population.