IMROZ - IsaRVd vs RVd in Newly Diagnosed Transplant Ineligible MM | Thierry Facon, MD | EHA 2024

I am Professor Thierry Facon from Lille University Hospital in France. So we report at the AHA the so-called EMRU study. This is a very large, phased-free, randomized, international study for transplant ineligible patients with newly diagnosed multiple myeloma. So the purpose of the study was to assess the clinical value of adding isatuximab, which is an anti-CD38 monoclonal antibody, to bortezomiblandalidomide and dexamethasone, the so-called VRED regimen. So VRED is a very well established type of care for newly diagnosed multiple myeloma patients, both the transplant eligible and the transplant ineligible. So these drugs are well-known. So proteasome inhibitors, especially bortezomiblandalidomide, and also CD38 monoclonal antibodies have been used in multiple myeloma for several years. So the study basically put together these three major drugs or drug families in the same regimen. So the study is a randomized study. So we randomly allocated 446 patients from 21 different countries in either isatuximab VRED followed by isatuximab RRED versus VRED followed by RRED. So these two regimens were continuous regimens given to progression. The primary endpoint was what we call progression-free survival. So basically the way to delay relapse in patients. So the study results were very positive in favor of isatuximab VRED for the PFS primary endpoint. The median PFS for the VRED arm was 54 months and the median PFS was not reached for the isatuximab VRED arm. So the five-year PFS rates were 45% for VRED versus 63% for isabRED. That's a very large and very clinically significant difference in terms of PFS. It means that combining isatuximab with VRED will delay relapse in a very significant way for many patients. So efficacy results have been great. This is also true for response. So we assess complete response, we assess MRD negativity. Complete response rates were 64% for VRED versus 75% for isabRED. MRD negativity, and you know MRD negativity is now something very important for patients, and MRD negativity was observed in more than 50% of patients. And MRD negativity in patients with complete response was seen in 55% of patients receiving the isabRED arm. What we call sustained MRD negativity, so the possibility to stay on an MRD negativity state for more than one year was seen in 47% of patients in the isabRED arm. So these are great study results in terms of response. So this regimen was able to provide deep responses in the vast majority of patients. Safety was good. This regimen was well tolerated. In fact, the tolerability of this regimen was basically the tolerability of each drug, the CD38, the bortezomib and the lenalidomide. And at the end of the day, and even so the study run during the pandemic, in fact, the safety was considered to be good. This regimen was considered to be well tolerated. So in summary, this EMOR study is the first study combining a CD38 with VRD for transport ineligible patients and patients enrolled in the EMOR study had an age between 65 years and 80 years. We did not enroll patients over the age of 80 years because we had in mind that these very elderly patients may not tolerate four drugs, so that was just to remain on the safe side. But at the end of the day, for these patients between the age of 65 years and 80 years, this combination of isabRED provide high-efficiency with a good safety and will likely establish this new regimen as a new standard of care for patients below the age of 80 years. The US FDA has provided accelerated review for this regimen. And I cannot speak for EMA, but I am quite confident that this regimen will be approved by FDA, EMA, and other regulatory agencies in the near future in many countries.