Thierry Facon, MD, on Multiple Myeloma: Results From the IMROZ Study on Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone

The purpose of the study was to assess the clinical benefit of adding isatuximab, which is an anti-CD38 monoclonal antibody to bortezomib lendalidomide and dexamethasone referred as the VRd regimen. So this study is the first study combining a CD38 monoclonal antibody to the VRd platform. And this study is conducted in transplant-ineligible patient with newly diagnosed multiple myeloma. Importantly, the VRd regimen is a very well-established standard of care for the elderly and also for transplant-eligible patients. And also importantly, these elderly patients have still an unmet medical need, and it's extremely important for this particular patient to have a very strong and effective first-line therapy. So the study was conducted as a phase III international study in 21 countries, and we enrolled 446 patients randomly allocated to either Isa-VRd, or VRd, followed by Isa-Rd, or Rd alone. The primary endpoint was progression-free survival. So the study met its primary endpoint of PFS with a very strong benefit in favor of the isatuximab arm. The median PFS was not reached for the Isa-VRd arm and was 54 months for the VRd arm. The five-year PFS rate was 45% for VRd versus 63% for Isa-VRd. The hazard ratio was 0.596. So this was both statistically and clinically a very significant difference. Besides this PFS benefit, we had also an important benefit in terms of response, including high quality responses. The complete response rate was 64% for VRd versus 75% for Isa-VRd. We assessed minimal residual disease. So MRD and MRD negativity was seen in MRD, negative CR was seen in 55% of the Isa-VRd patients versus 41% of the VRd patients. Sustained MRD negativity for more than one year was almost double in the Isa-VRd arm from 24% to 47%. In terms of safety, this regimen was well-tolerated. The safety profile was in line with the safety profiles of each agent, and these agents are known for many years. So we did not see any new safety signal, and the safety of this regimen was considered to be good for this elderly patient. Also, considering that we did exclude patients over the age of 80 years. The conclusion is just to say that this Isa-VRd regimen will become likely a new standard of care for transplant-ineligible patients below the age of 80 years. So this is an important result based on a very strong efficacy and an adequate safety profile.