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The European Commission (EC) has granted approval to isatuximab-irfc (Sarclisa) in combination with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (Isa-VRd) as induction therapy for adult patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant (ASCT).1
This decision follows the positive opinion granted by the European Medicines Agency’s Committee for Medicinal Products for Human Use in June, 2025.
Results from part 1 of the phase 3 German-speaking Myeloma Multicenter Group (GMG)-HD7 study (NCT03617731) supported the European Union (EU) approval. In this trial, Isa-VRd met the primary end point of part 1, improved minimal residual disease (MRD)–negativity rates at the end of the 18-week induction period, in transplant-eligible patients with newly diagnosed multiple myeloma.
The data, which were published in the Journal of Clinical Oncology, also showed a complete response (CR) rate of 43.5% with Isa-VRd (n = 331) vs 34.0% for VRd alone (n = 329; OR, 1.49; 95% CI, 1.08-2.07; P = .013).2 Following ASCT, the MRD-negativity rates were 66.2% and 47.7%, respectively (OR, 2.13; 95% CI, 1.56-2.92; P < .0001).
Both CR and MRD-negative status were achieved by 38.1% of patients in the Isa-VRd arm and 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, excepting patients with a World Health Organization (WHO) performance status greater than 1, revised International Staging System stage III disease, or high-risk cytogenetics.
“We have been on a mission to accelerate [isatuximab]’s clinical development program with the hope to bring this important medicine to as many people as possible living with multiple myeloma,” Olivier Nataf, Global Head of Oncology at Sanofi, stated in a news release.1 “Today’s decision represents a prime example of those efforts, and most importantly, paves the way for [isatuximab] to potentially become accessible to even more patients in the EU, regardless of transplant eligibility or line of therapy.”
With this regulatory approval, isatuximab now holds 4 approved indications globally and is approved across all lines of therapy in the European Union, regardless of transplant eligibility, according to Sanofi.
GMMG-HD7 Trial Overview
GMMG-HD7 is a pivotal, randomized, open-label, multicenter, two-part trial designed to independently assess the effects of Isa-VRd during the induction and maintenance phases, followed by post-transplant re-randomization to isatuximab plus lenalidomide in transplant-eligible, newly diagnosed multiple myeloma.1
A total of 662 patients were enrolled onto the trial across 67 sites in Germany. Eligible patients were between 18 to 70 years of age with a confirmed diagnosis of untreated multiple myeloma requiring systemic therapy, were candidates for high-dose therapy ASCT, and had a WHO performance status of 0 to 2.3
In part one of the trial, patients were randomly assigned to receive 3, 42-day cycles of induction therapy with VRd with or without isatuximab. In the investigational arm, isatuximab was administered intravenously at 10 mg/kg on days 1, 8, 15, 22, and 29 of cycle 1, and on days 1, 15, and 29 of cycles 2 and 3.1,3 All patients then proceeded to intensification per GMMG standard, including stem cell mobilization and ASCT. After intensification, patients were randomized a second time to receive maintenance therapy with either lenalidomide alone or in combination with isatuximab for up to 3 years.
The study’s co-primary end points are MRD negativity following induction, assessed via next-generation flow cytometry at a sensitivity threshold of 10⁻⁵, and progression-free survival (PFS) following the second randomization. Secondary end points include CR rate, overall survival (OS), PFS from the first randomization, and safety.
Additional Efficacy and Safety Data
MRD findings in part 1 of the GMMG-HD7 study were supported by the final PFS analysis.2 The median PFS was not reached in either arm, but a statistically significant improvement favored the Isa-VRd arm vs VRd alone (HR, 0.7; 95% CI, 0.52-0.95; stratified log-rank P = .0184).
Landmark analyses further demonstrated that MRD negativity was associated with significantly prolonged PFS from both the end of induction (HR, 0.38; 95% CI, 0.26-0.55; P < .001) and the end of transplant (HR, 0.42; 95% CI, 0.28-0.63; P < .001) compared with MRD positivity. Among MRD-negative patients, PFS from the end of induction was comparable between treatment arms (P = .72). However, in patients with MRD-positive disease, Isa-VRd significantly extended PFS vs VRd alone (HR, 0.64; 95% CI, 0.43-0.96; P = .03). PFS from the end of transplant did not significantly differ between treatment arms for either MRD-negative (P = .882) or MRD-positive (P = .314) subgroups.
From the start of maintenance therapy, patients with continued MRD negativity had significantly prolonged PFS vs those without (HR, 0.41; 95% CI, 0.25-0.65; P < .001). Among patients with sustained MRD negativity, PFS did not differ by treatment arm (P= .77). In patients without sustained MRD negativity, there was a trend toward improved PFS with isatuximab plus VRd, though this 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 analysis (stratified log-rank v = .548).
Regarding safety, Isa-VRd demonstrated a manageable and consistent safety profile, according to prior findings from an interim analysis of GMMG-HD7.
Data from part 2 of the GMMG-HD7 study, which evaluates the maintenance phase, are pending.1 These findings contribute to the growing body of clinical evidence supporting the use of isatuximab in the frontline setting, Sanofi concluded in the news release.
References
- Sanofi’s Sarclisa approved in the EU for the treatment of transplant-eligible newly diagnosed multiple myeloma. News release. Sanofi. July 25, 2025. Accessed July 25, 2025.https://www.sanofi.com/en/media-room/press-releases/2025/2025-07-25-05-00-00-3121591
- Mai EK, Bertsch U, Pozek E, et al. Isatuximab, lenalidomide, bortezomib, and dexamethasone induction therapy for transplant-eligible newly diagnosed multiple myeloma: final part 1 analysis of the GMMG-HD7 trial. J Clin Oncol. 2025;43(11):1279-1288. doi:10.1200/JCO-24-02266
- Trial on the effect of isatuximab to lenalidomide, bortezomib/dexamethasone (RVd) induction and lenalidomide maintenance in patients with newly diagnosed myeloma (GMMG HD7). ClinicalTrials.gov. Updated January 24, 2025. Accessed Accessed July 25, 2025. https://www.clinicaltrials.gov/study/NCT03617731