THE IMROZ Phase III trial has brought promising news for patients who are transplant-ineligible with newly diagnosed multiple myeloma (NDMM). The trial evaluated the efficacy and safety of a novel combination therapy, isatuximab, bortezomib, lenalidomide, and dexamethasone (Isa-VRd), against the current standard of care, VRd. Findings from this trial were presented at ASCO 2024.
For patients with NDMM, particularly those who are elderly or have comorbidities precluding them from transplant, the first line of treatment is crucial. In this global, prospective, randomized, open-label study conducted across 102 sites in 21 countries, 446 patients were stratified and randomized in a 3:2 ratio to receive either Isa-VRd or VRd.
The Isa-VRd regimen included isatuximab (10 mg/kg IV), along with the standard VRd doses: bortezomib (1.3 mg/m² SC), lenalidomide (25 mg PO), and dexamethasone (20 mg IV/PO). The primary endpoint was progression-free survival (PFS), with secondary endpoints including complete response (CR), minimal residual disease negativity (MRD-), and overall survival.
As of the data cutoff on September 26, 2023, the median follow-up was 59.7 months. Notably, the Isa-VRd arm showed a median treatment duration of 53.2 months versus 31.3 months for VRd. At this point, the median PFS for Isa-VRd had not been reached, whereas it was 54.3 months for VRd (HR 0.596, 98.5% CI 0.406–0.876, p=0.0005). Projections suggest Isa-VRd could achieve a median PFS of approximately 90 months.
The PFS benefit was consistent across various subgroups and sustained through subsequent lines of therapy (PFS2 HR 0.697, 95% CI 0.51-0.952). Importantly, the safety profile of Isa-VRd was in line with expectations, with exposure-adjusted Grade 5 treatment-emergent adverse event rates of 0.03 (Isa-VRd) versus 0.02 (VRd).
The IMROZ study marks a significant advancement, demonstrating that Isa-VRd significantly reduces the risk of progression or death by 40.4% compared to VRd, while also providing deep and sustained responses. These findings endorse Isa-VRd as a potential new standard of care for NDMM patients ineligible for transplant, offering hope for improved long-term outcomes in this challenging patient population.
Reference: Facon T et al. Phase 3 study results of isatuximab, bortezomib, lenalidomide, and dexamethasone (Isa-VRd) versus VRd for transplant-ineligible patients with newly diagnosed multiple myeloma (IMROZ). Abstract 7500. American Society of Clinical Oncology 2024.
