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.