Isa-VRd Significantly Improves Survival vs VRd in Transplant-Eligible Myeloma

Microscopic photorealistic image of myeloma cells - Generated with Google Gemini AI

The addition of isatuximab (Sarclisa) to standard-of-care lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (isa-VRd) induction therapy followed by hematopoietic cell transplant (HCT) significantly improved progression-free survival (PFS) vs VRd alone among patients with HCT-eligible, newly diagnosed multiple myeloma.¹

Full results from part 2 of the German-speaking Myeloma Multicenter Group (GMMG)-HD7 phase 3 study (NCT03617731)will be presented at an upcoming medical meeting.

“Successful induction therapy is one of the most critical components to reduce the relapse or recurrence risk in patients with newly diagnosed multiple myeloma. 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. These data provide evidence that the isa-RVd regimen potentially improves progression-free survival 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,” said Hartmut Goldschmidt, MD, president of GMMG, professor of medicine at Heidelberg University Hospital, and principal investigator of the study, in a press release.

In 2021, findings from part 1 of the GMMG-HD7 trial were presented and showed that isa-VRd significantly increased the rate of MRD negativity vs VRd, meeting the primary end point of the study.2After 18 weeks of induction, the MRD negativity rate in the isa-VRd arm (n = 331) was 50.1% vs 35.6% in the VRd arm (OR, 1.83; 95% CI, 1.34-2.51; P <.001).

The safety profile of isatuximab was consistent with previous reports, and no new safety signals were identified from this part of the study. This was the first phase 2 study to evaluate MRD negativity following induction as a primary end point, and MRD is strongly associated with improved patient outcomes.

Further, findings from the phase 3 IMROZ trial (NCT03319667) of isa-VRd in patients with transplant-ineligible multiple myeloma presented at the 2024 American Society of Clinical Oncology Annual Meeting showed that, at a median follow-up of 59.7 months, patients treated with isa-VRd (n = 265) followed by isa-Rd experienced a median PFS that was not reached (NR) compared with 54.34 months (95% CI, 45.207-NR) in patients treated with VRd alone (HR, 0.596; 98.5% CI, 0.406-0.876; log-rank P = .0005). The 60-month PFS rate was 63.2% in the investigational group vs 45.2% in the control arm, and this PFS benefit was seen across most subgroups.³

In May 2024, the FDA granted priority review to the supplemental biologics license application of isa-VRd in transplant-ineligible multiple myeloma, supported by findings from the IMROZ trial.⁴ The Prescription Drug User Fee Act target action date is September 27, 2024.

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 8, 2024. https://tinyurl.com/mrybjfhm 

2. Sarclisa® (isatuximab) trial is first phase 3 study to meet primary endpoint of minimal residual disease negativity in transplant-eligible patients with newly diagnosed multiple myeloma. News release. Sanofi. December 11, 2021. Accessed August 8, 2024. https://tinyurl.com/56szzf2n 

3. Facon T, Dimopoulos MA, Leleu XP, et al. Phase 3 study results of isatuximab, bortezomib, lenalidomide, and dexamethasone (Isa-VRd) versus VRd for transplant-ineligible patients with newly diagnosed multiple myeloma (IMROZ). J Clin Oncol. 2024;42(suppl 16):7500. doi:10.1200/JCO.2024.42.16_suppl.7500

4. Sarclisa accepted for FDA priority review for the treatment of transplant-ineligible newly diagnosed multiple myeloma. News release. Sanofi. May 27, 2024. Accessed August 8, 2024. https://tinyurl.com/53hhdwwj