Isatuximab plus bortezomib, lenalidomide, and dexamethasone for transplant-ineligible newly diagnosed multiple myeloma patients: a frailty subgroup analysis of the IMROZ trial.

Abstract

Patients with multiple myeloma meeting frailty criteria have worse outcomes than those identified as non-frail. Here, we present a post-hoc subgroup analysis of IMROZ, a global, phase III, open-label study investigating isatuximab (Isa) with bortezomib, lenalidomide, and dexamethasone (VRd) followed by Isa-Rd (n=265) versus VRd followed by Rd (n=181) in newly diagnosed transplant-ineligible multiple myeloma (Ti NDMM) patients using the simplified International Myeloma Working Group (sIMWG) frailty score. Although patients aged >80 were excluded, there was no exclusion for patients meeting frailty criteria. All patients received standard VRd/Rd dosing; Isa-VRd patients received intravenous Isa (cycle 1, 10 mg/kg QW; cycles 2-17, Q2W; subsequent cycles, Q4W). Patients with a frailty score of 0/1 were considered non-frail; scores ≥2 were frail. Using this scoring, 26.7% of patients were frail (26.0% Isa-VRd; 27.6% VRd), and 72.0% non-frail (72.8% Isa-VRd; 70.7% VRd). After a median follow-up of 59.7 months, Isa-VRd significantly improved progression-free survival versus VRd in frail patients (hazard ratio [HR] 0.518; 95% confidence interval [CI] 0.294-0.912, P=0.0227) and non-frail patients (HR 0.615; 95% CI 0.419-0.903, P=0.0131). Significantly more frail patients receiving Isa-VRd than VRd achieved minimal residual disease negativity and complete response (odds ratio 3.459 [95% CI 1.495-8.006], P=0.0030, 10-5 by next-generation sequencing). Rates of treatment-emergent adverse events leading to definitive discontinuation were similar between both arms regardless of frailty status. This post-hoc subgroup analysis of the IMROZ trial demonstrated that Isa-VRd is an effective option with a manageable safety profile for frail patients with Ti NDMM.