Isa-VRd Improves Outcomes in Frontline Myeloma: Phase 3 IMROZ Results From ASCO and EHA

The phase 3 IMROZ trial, which evaluated isatuximab in combination with bortezomib, lenalidomide, and dexamethasone (Isa-VRd), was a featured presentation at both the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and the European Hematology Association (EHA) Congress. The trial’s findings represent a major advancement in frontline therapy for patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for, or not intended to proceed with, autologous stem cell transplantation.

At ASCO 2024, Dr. Thierry Facon presented the primary analysis of the IMROZ trial of 446 transplant-ineligible patients with NDMM. Patients were randomized to receive Isa-VRd or standard VRd, with the primary endpoint of progression-free survival (PFS). [Facon 2024a]

Isa-VRd reduced the risk of disease progression or death by 40% compared with VRd alone. Minimal residual disease (MRD)–negative complete responses were achieved in 55.5% of patients receiving the quadruplet regimen compared with 40.9% in the control arm with 46.8% of the Isa-VRd–treated patients maintaining MRD negativity for at least 12 months versus 24.3% of those on VRd. Adverse events were more frequent in the Isa-VRd arm but were consistent with the known safety profiles of the component drugs. These results were simultaneously published in The New England Journal of Medicine and widely regarded as a practice changing option for patients. [Facon 2024b]

At EHA 2024, the IMROZ data were revisited with extended subgroup analyses and additional discussion on clinical implications. Presenters confirmed the consistency of benefit observed in ASCO, with efficacy preserved across multiple patient subsets, including older adults and those with high-risk cytogenetics. The high rates of sustained MRD negativity continued to support the use of MRD as a meaningful endpoint in both trials and practice. [Facon 2024c]

The results support a growing body of evidence regarding quadruplet induction for transplant-ineligible patients. The data are currently under regulatory review by both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for a potential label expansion of isatuximab in the frontline, transplant-ineligible setting.

Facon T, Beksac M, Mohty M, 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). Presented at: 2024a American Society of Clinical Oncology Annual Meeting; May 31–June 4, 2024; Chicago, IL. Abstract 7500. doi:10.1200/JCO.2024.42.16_suppl.7500

Facon T, Beksac M, Mohty M, et al. Isatuximab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2024b;391(17):1597-1609. doi:10.1056/NEJMoa2400712

Facon T, Beksac M, Mohty M, 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). Presented at: 29th Congress of the European Hematology Association; June 13–16, 2024c; Madrid, Spain. Abstract S100.