2 Clarke Drive
Suite 100
Cranbury, NJ 08512
© 2025 MJH Life Sciences™ and OncLive - Clinical Oncology News, Cancer Expert Insights. All rights reserved.
CHMP issues positive opinion for isatuximab plus VRd in transplant-eligible, newly diagnosed multiple myeloma.
Multiple Myeloma | Image
Credit: © LASZLO -
stock.adobe.com
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has issued a positive opinion recommending the approval of isatuximab (Sarclisa) in combination with bortezomib (Velcade), lenalidomide, and dexamethasone (VRd) for the induction treatment of adult patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant (ASCT).¹
The recommendation is based on findings from part 1 of the phase 3 GMMG-HD7 trial (NCT03617731), data from which were presented at the 2024 ASH Annual Meeting and published in the Journal of Clinical Oncology.2 Results demonstrated that the addition of isatuximab to VRd (n = 331) produced a complete response (CR) rate of 43.5% vs 34.0% for VRd alone (n = 329; odds ratio [OR], 1.49; 95% CI, 1.08-2.07; P = .013). After ASCT, the minimal residual disease (MRD)–negativity rates were 66.2% and 47.7%, respectively (OR, 2.13; 95% CI, 1.56-2.92; P < .0001).
A total of 38.1% of patients in the Isa-VRd arm achieved both CR and MRD-negative status compared with 25.8% in the VRd arm (OR, 1.76; 95% CI, 1.25-2.50; P = .001). Preplanned exploratory analyses showed consistent MRD-benefit across most subgroups, with the exception of patients with a WHO performance status of more than 1, revised International Staging System stage III disease, or high-risk cytogenetics. The median progression-free survival (PFS) was not reached in both arms, but the difference reached statistical significance favoring the isatuximab arm (HR, 0.7; 95% CI, 0.52-0.95; stratified log-rank P = .0184).
“The CHMP’s recommendation represents significant progress toward our ambition for [isatuximab] addressing unmet patient needs in multiple myeloma care and making a meaningful difference in treatment outcomes at every stage of the disease across regions," Olivier Nataf, global head of Oncology at Sanofi, stated in a news release.1 "If approved, this regimen would represent a new, important induction option for transplant-eligible patients, with the potential to improve long-term outcomes and deepen responses at a critical juncture in treatment.”
The GMMG-HD7 study is an ongoing, multicenter, randomized, open-label, phase 3 trial initiated by the German-Speaking Myeloma Multicenter Group (GMMG) in collaboration with Sanofi.1 Designed to evaluate the efficacy of isatuximab in the transplant-eligible, newly diagnosed multiple myeloma (NDMM) population, the trial enrolled 662 patients across 67 sites in Germany. Patients needed to be 18 to 70 years of age with newly diagnosed multiple myeloma requiring systemic therapy and eligible for ASCT.2,3
In the first part of the trial, patients were randomly assigned to receive 3 42-day cycles of induction therapy with VRd, with or without isatuximab. In the experimental arm, isatuximab was administered intravenously at a dose of 10 mg/kg on days 1, 8, 25, 22, and 29 of cycle 1, then days 1, 15, and 29 of cycles 2 and 3.2 All patients subsequently proceeded to intensification therapy per GMMG standard, including stem cell mobilization and ASCT.
Following intensification, patients underwent a second randomization to receive maintenance therapy with either lenalidomide alone or lenalidomide plus isatuximab for up to 3 years.
The co-primary end points of the study are MRD negativity after induction therapy, assessed using next-generation flow cytometry at a sensitivity of 10⁻⁵, and PFS following the second randomization. Additional key secondary end points include CR rate, overall survival (OS), PFS from the first randomization, and safety.
Landmark analyses further demonstrated that patients achieving MRD negativity experienced significantly prolonged PFS from the end of induction (HR, 0.38; 95% CI, 0.26-0.55; P < .001) and end of transplant (HR, 0.42; 95% CI, 0.28-0.63; P < .001) compared with MRD-positive patients. PFS from the end of induction was similar among MRD-negative patients in both arms (P = .72), and isatuximab plus VRd conferred significantly longer PFS among MRD-positive patients compared with VRd (HR, 0.64; 95% CI, 0.43-0.96; P = .03). PFS from the end of transplant did not differ significantly between treatment arms for either MRD-negative (P = .882) or MRD-positive (P = .314) patients.
In analyses beginning at the start of maintenance therapy, PFS was significantly prolonged in patients with continued MRD negativity compared with those without (HR, 0.41; 95% CI, 0.25-0.65; P < .001). Among patients with continued MRD negativity, PFS was similar between the isatuximab and VRd arms (P = .77). For patients without continued MRD negativity, PFS from the start of maintenance tended to favor the isatuximab arm, though the difference did not reach statistical significance (HR, 0.68; 95% CI, 0.41-1.13; P = .14).
OS data were not mature at the time of this analysis (stratified log-rank test P = .548).
Related Content: