Despite significant improvements in the survival of multiple myeloma (MM) patients over the past two decades, thanks to the emergence of new drugs and therapies, the prognosis for those not eligible for bone marrow transplantation remains relatively poor. Therefore, there is an urgent need to explore new treatment options to improve their outcomes. At the recently held 29th Annual Congress of the European Hematology Association (EHA 2024), Professor Thierry Facon, a member of the International Myeloma Working Group (IMWG) and from the University of Lille, CHU Lille, Service des Maladies du Sang, Lille, France, presented the key findings of the IMROZ study in an oral report. This study explored the efficacy of isatuximab combined with the VRD regimen (Isa-VRD) in treating newly diagnosed MM patients not suitable for transplantation, and the results were published in the New England Journal of Medicine (NEJM) in early June this year. "Oncology Frontier-Hematology Frontier" specially invited Professor Thierry Facon to share the important findings and significance of the IMROZ study at the venue.Oncology Frontier-Hematology Frontier：At this EHA conference, you reported the breakthrough results of IMROZ research. Firstly, could you please introduce the background and main design of this study?
Professor Thierry Facon：The IMROZ study is a very large, phase three, randomized international study designed for newly diagnosed transplant-ineligible patients with multiple myeloma. The purpose of the study was to assess the clinical value of adding isatuximab, an anti-CD38 monoclonal antibody, to the VRD regimen (bortezomib, lenalidomide, and dexamethasone). We enrolled 446 patients below the age of 80 years, who were randomly allocated to either VRd or isatuximab VRd , with progression-free survival (PFS) as the primary endpoint.
Oncology Frontier-Hematology Frontier：In the IMROZ study, the Isa VRD regimen significantly extended the progression free survival (PFS) of patients compared to the VRD regimen. Can you explain in detail the advantages of this treatment combination? What is its therapeutic mechanism?
Professor Thierry Facon：The primary endpoint of PFS was met with a median follow-up of approximately five years. The median PFS was not reached for the isatuximab VRD arm and was 54 months for the VRD arm. The five-year PFS rates were 45% for VRD and 63% for isatuximab VRD. The hazard ratio was 0.59, representing a 40% reduction in the risk of progression or death.That’s a very clinically significant and very statistically significant difference between the two arms.
Besides the PFS, we had some key secondary endpoints, especially complete response or better, and MRD negativity. So in the isatuximab VRd arm, almost 75% of patients achieved a complete response or better compared to 64% of patients in the VRd arm. MRD-negative complete response was seen in 55.5% of patients in the isatuximab VRd arm versus 41% of patients in the VRd arm. And most importantly, we looked at sustained MRD negativity, and sustained MRD negativity was almost double in the isatuximab VRd arm, from 24% in the VRd arm to 47% in the isatuximab VRd arm. So this isatuximab VRd regimen was associated with deep response rates, including MRD negativity and sustained MRD negativity.
Oncology Frontier-Hematology Frontier：The IMROZ study not only focuses on the progression free survival of patients, but also on the safety of treatment and the quality of life of patients. Could you please introduce how the Isa-VRD protocol performs in terms of safety in the IMROZ study? What is the incidence of adverse reactions compared to VRD? Has the patient’s quality of life improved?
Professor Thierry Facon：The safety profile of isatuximab VRD was favorable and well-tolerated. There was no difference in terms of quality of life between the two arms.I should also have said that for survival, overall survival is still immature, but with a trend in favor of isatuximab VRd, the five-year survival is 65% for VRd versus 72% for isatuximab VRd, representing a 22% reduction in the risk of death. Although there were slightly more grade 3 or higher adverse events and grade 5 adverse events in the isatuximab VRD arm, this was likely due to the longer treatment duration. The median treatment duration was 31 months for VRD versus 53 months for isatuximab VRD. When looking at exposure-adjusted incidence rates, they were somewhat similar between the two arms.
Oncology Frontier-Hematology Frontier：What new development directions do you think will be in the field of multiple myeloma treatment in the future? Can we expect more effective treatment options to emerge for NDMM patients who are not suitable for transplantation?
Professor Thierry Facon：The IMROZ study will establish isatuximab VRD as a new standard of care for elderly patients with newly diagnosed multiple myeloma not eligible for transplant. This is a significant achievement, with the median PFS likely exceeding 80 months in this population. Future developments may include the use of bispecific antibodies and CAR T-cell therapies, even for elderly patients, as we continue to improve treatment options and outcomes.
Oncology Frontier-Hematology Frontier：I would like to ask you the final question.What do you think about Chinese doctors and clinics? What do you want to say to them?
Professor Thierry Facon：Okay. I know your country quite well. I did many meetings in China. I will be in Shanghai at the end of this month, and I will likely be back to China before the end of the year. I have visited, let’s say, something like 30 different cities in China in the past 15 years.The good point is that your point is well taken because IMROZ has Chinese patients, Chinese centers. As you know, the study has been published early June in the New England Journal of Medicine, and one co-author is from Shenyang, from your country.
The study I have presented this morning at the press meeting and I will present at the plenary session tomorrow, includes Chinese patients. So we have 12 patients in this ITT population, but China also had an extension study. 12 patients are in IMRO, and an additional 38 patients have been treated in a different Chinese study. This means that basically there is a group of 50 Chinese patients having received either VRd or isatuximab VRd in the context of this similar study. So that will likely lead to approval by the Chinese FDA, so the study is important for China in many ways, but it’s also a good opportunity to congratulate and thank Chinese investigators.
