At the 2024 annual meeting of the American Society of Clinical Oncology (ASCO), Thierry Facon, MD, presented results from the phase 3 IMROZ study evaluating the addition of the anti-CD38 monoclonal antibody isatuximab to bortezomib (V), lenalidomide (R), and dexamethasone (d) compared to VRd alone in patients with newly diagnosed multiple myeloma (NDMM) who were ineligible for an autologous hematopoietic stem cell transplant (ASCT).
The global study randomly assigned 446 patients 80 years or younger to induction therapy with isatuximab-VRd (Isa-VRd) followed by maintenance therapy with isatuximab-Rd (n=265) or VRd followed by Rd maintenance (n=181). Maintenance therapy was continued until progressive disease, unacceptable toxicity, or patient withdrawal from the study. The primary endpoint was progression-free survival (PFS).
Median patient age on the study was 72 years. The majority of patients had revised international staging system (R-ISS) stage I or II (88% with Isa-VRd vs 87% with VRd) and standard-risk cytogenetics(78% with Isa-VRd vs 77% with VRd).
With a median follow-up of approximately 5 years, the addition of isatuximab to VRd and Rd maintenance resulted in a statistically significant improvement in PFS compared to VRd followed by Rd (median PFS not reached vs 54 months; HR 0.596, P<.0001), representing a 40% reduction in the risk of progression or death. The PFS benefit was observed across most subgroups analyzed, however, the PFS hazard ratio for those patients with high-risk cytogenetics at baseline was 0.971 (95%CI: 0.481-1.96). (Table 1)
The addition of isatuximab to VRd also led to deeper responses, with significant improvements in complete response (CR) rates or higher (75% vs 64%), minimal residual disease (MRD) negative rates in the intent-to-treat population (58% vs 44%), and those with a CR (56% vs 41%), and sustained MRD negativity for 1 year or more (47% vs 24%) compared to VRd. Overall survival at 5-years was 72% vs 66% with isa-VRd and VRd, respectively, but longer follow up is needed. Quality of life scores were similar between the arms. (Table 1)
Safety was generally consistent with the known profiles of the individual drugs. Neutropenia and infections were common. (Table 2)
The combination of Isa-VRd followed by Isa-Rd provides an important new treatment option for patients with NDMM who are not eligible for ASCT. The presented results were published simultaneously in the New England Journal of Medicine. Longer follow-up is needed to determine the impact of isatuximab on overall survival.
Facon T, et al. J Clin Oncol. 2024;42 (suppl 16): abstract 7500.
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