Isatuximab/VRd Improves PFS vs VRd Alone in Transplant-Eligible NDMM

Investigators will present full results from the phase 3 GMMG-HD7 trial at a future medical meeting.

The addition of anti-CD38 monoclonal antibody, isatuximab (Sarclisa), to bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd) as induction therapy improved progression-free survival (PFS) vs VRd alone in patients with newly diagnosed multiple myeloma (NDMM) eligible to undergo transplantation, according to a press release on findings from the phase 3 GMMG-HD7 trial (NCT03617731).¹

Treatment with isatuximab plus bortezomib elicited a statistically significant and clinically meaningful reduction in the risk of disease progression or death. Investigators plan to present full results from the GMMG-HD7 trial at a future medical meeting.

“Successful induction therapy is one of the most critical components to reduce the relapse or recurrence risk in patients with [NDMM]. While we observed this investigational combination showed improved minimal residual disease [MRD] negativity rates in the bone marrow, indicating potentially deeper responses after induction, further follow-up was needed to better understand how this translated to long-term outcomes,” lead investigator Hartmut Goldschmidt, MD, president of German-speaking Myeloma Multicenter Group, a professor of medicine at Heidelberg University Hospital in Germany, said in the press release.¹ “These data provide evidence that the [isatuximab plus] RVd regimen potentially improves [PFS] in the frontline, transplant-eligible population and supports the potential of this quadruplet to become a new standard-of-care induction regimen in this treatment setting.”

The GMMG-HD7 trial findings build upon previously reported data from the phase 3 IMROZ trial (NCT03319667), which assessed isatuximab plus VRd in patients with NDMM who are ineligible to undergo transplantation. Updated findings from IMROZ were published in the New England Journal of Medicine.²

Results from the trial showed that estimated PFS was 63.2% in the isatuximab/VRd group vs 45.2% in the VRd group at 60 months (HR, 0.60; 98.5% CI, 0.41-0.88; P < .001). A complete response (CR) was observed in 74.7% of the isatuximab/VRd group vs 64.1% in the VRd group (P = .01); MRD-negative status with a CR was observed in 55.5% and 40.9%, respectively (P = .003). Furthermore, treatment with isatuximab/VRd had a similar safety profile compared with the VRd regimen alone, with no new safety signals observed with the combination therapy.

“The significant [PFS] benefit observed with [isatuximab] combination therapy compared [with] VRd is important and encouraging for patients with [NDMM],” lead investigator Thierry Facon, MD, professor of hematology in the Department of Hematology at Lille University Hospital in Lille, France, and a member of the French Academy of Medicine, stated in a news release on the study findings.³ “Effective frontline therapy has the potential to modify the course of the disease, which is a key outcome for transplant-ineligible patients who often [have] high rates of attrition in later lines of therapy. The IMROZ results demonstrate the promise of [isatuximab] as a backbone to frontline therapy, which may improve long-term outcomes for this incurable disease.”

Patients were enrolled from December 2017 to March 2019. Investigators of the phase 3 trial randomly assigned 446 adult patients with symptomatic previously untreated myeloma 3:2 to receive either isatuximab plus VRd (n = 265) or VRd alone (n = 181). Assignment was stratified based on country, age, or classification of disease stage.

The primary end point of the study was PFS. Key secondary end points included CRs or better, MRD-negative status in patients with a CR or better, a very good partial response, and overall survival (OS).

Within the isatuximab/VRd and VRd groups, 47.2% and 24.3% of patients were receiving treatment as of the cut-off date of September 26, 2023. The median treatment duration was 53.2 months (range, 0.5-68.8) and 31.3 (range, 0.6-67.2) months in the isatuximab/VRd and VRd arms, respectively, with the median number of cycles being 52 (range, 1-69) and 29 (range, 1-69).

Disease progression or death occurred in 31.7% of the isatuximab/VRd group. Additionally, the time to disease progression was longer in the isatuximab-VRd arm than the VRd arm (HR, 0.41; 95% CI, 0.29-0.60).

References

1. Sarclisa induction treatment demonstrated significantly improved progression-free survival in patients with newly diagnosed multiple myeloma eligible for transplant. News release. Sanofi. August 8, 2024. Accessed August 9, 2024. https://tinyurl.com/4e8sy4pv
2. Facon T, Dimopoulos MA, Leleu XP, et al. Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. Published online June 3, 2024. doi:10.1056/NEJMoa2400712
3. ASCO: Sarclisa is first anti-CD38 to significantly improve progression-free survival in combination with VRd for newly diagnosed transplant-ineligible multiple myeloma in phase 3. News release. Sanofi. June 3, 2024. Accessed August 7, 2024. https://tinyurl.com/5exfukej