Multicenter Open Label Phase 3 Study of Isatuximab Plus Lenalidomide and Dexamethasone With/Without Bortezomib in the Treatment of Newly Diagnosed Non Frail Transplant Ineligible Multiple Myeloma Elderly Patients (≥ 65; < 80 Years).

Overall the issue of patients above 65-70 years of age being that it is impossible for most of them to undergo an intensive treatment like autologous stem cell transplant with little prospect of debulking effectively the bone marrow with chemotherapy, and also few possibilities to harass the bone microenvironment in the tumoral niche. If, advanced age in frail patients is predictive of an increased risk of treatment-related toxicity, there is a growing number of elderly patients in regards to transplantation, but still fit if one considers the objectives of life characterized with prolonged survival. These patients might have the same treatment as to the transplant eligible, but without the transplant procedure. The development of immunotherapy has transformed the treatment landscape of cancer, particularly in MM, increasing the treatment possibilities with possibly fewer adverse events. The therapeutic strategy and treatment options for NTE patients moved from melphalan-based induction regimens to lenalidomide-based associations, which is now the backbone of most treatment for NTE patients. Even though the latest melphalan, bortezomib and prednisone (MPV) association was considered somewhat effective it was not so well tolerated. Furthermore, MPV hardly prolonged PFS beyond 2 years. It was recently improved with the addition of Daratumumab, first in class anti CD38 Mab in the phase III ALCYONE. The association lenalidomide and dexamethasone (Rd) has significantly improved the easiness of treating the NTE population and all drugs seem to be possible to combine to Rd. In that extent, proteasome inhibitors have always been one of the most impactful family of agents in MM, and as expected Bortezomib plus Rd has become a very relevant and commonly used regimen in NTE NDMM. These groundbreaking results have favored the development of 2 randomized phase 3 studies for registration of combination of antiCD38Mab (Daratumumab (Cepheus, NCT03652064), Isatuximab (Imroz, NCT03319667) +Rd +Velcade in comparison to VRd. Both studies have used as a comparator the VRd regimen which is today one of the safest, active and popular triplet based Rd regimen, approved, and therefore the best control arm possibly for these studies. However, as much as there has been no direct head to head comparison of VRd to Dara Rd, when looking at the data from Maia it is anticipated that DRd will become a standard of care, and might challenge strongly VRd. Yet, multiple questions remain still, anticipating the change in backbone from VRd to antiCD38 +Rd becoming the new standard of care for NTE NDMM patients. The investigators have therefore planned to answer the critical question of the role of proteasome inhibitors in NTE non frail NDMM when considering anti CD38 +Rd as the backbone.

NCT Number	NCT04751877
Lead Sponsor	Poitiers University Hospital Collaborators: Intergroupe Francophone du Myelome, Sanofi
Conditions	Multiple Myeloma, Myeloma
Enrollment	270 participants
Start Date	2021-07-17
Primary Completion	2024-06-18 (estimated)
Study Completion	2027-08-17 (estimated)
Updated on ClinicalTrials.gov	2026-02-10