RCT: Isatuximab Plus VRd Significantly Improves Progression-Free Survival in Newly Diagnosed Multiple Myeloma – N Engl J Med

Study Design and Population: This international, open-label, phase 3 trial assessed the efficacy of adding isatuximab to the bortezomib, lenalidomide, and dexamethasone (VRd) regimen in 446 patients aged 18 to 80 years with newly diagnosed multiple myeloma who were ineligible for transplantation. Participants were randomized in a 3:2 ratio to receive either the isatuximab-VRd combination or VRd alone.

Main Findings: At a median follow-up of 59.7 months, the isatuximab-VRd group showed a significantly higher estimated progression-free survival at 60 months (63.2% vs. 45.2%; HR, 0.60; P<0.001) compared to the VRd group. Additionally, the isatuximab-VRd group had higher rates of complete response or better (74.7% vs. 64.1%; P=0.01) and MRD-negative status with a complete response (55.5% vs. 40.9%; P=0.003). Safety profiles were comparable between the two groups.

Implications for Practice: The addition of isatuximab to the standard VRd regimen significantly improves progression-free survival and response rates in newly diagnosed multiple myeloma patients who are ineligible for transplantation, without increasing serious adverse events. This suggests that isatuximab-VRd may be considered a new standard of care in this patient population.

Reference: Facon, T., Dimopoulos, M.-A., Leleu, X. P., Beksac, M., Pour, L., Hájek, R., Liu, Z., et al. (2024). Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. New England Journal of Medicine, 390(24), 2311-2322. DOI: 10.1056/NEJMoa2400712.