Isatuximab Plus VRd Improves PFS in Transplant-Eligible, Newly Diagnosed Myeloma

Induction therapy with isatuximab-irfc (Sarclisa) in combination with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (Isa-VRd) led to a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with RVd alone, irrespective of maintenance regimen, in patients with transplant-eligible, newly diagnosed multiple myeloma, according to data from the phase 3 GMMG HD7 trial (NCT03617731).¹

Full data from the study 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,” Hartmut Goldschmidt, MD, president of German-speaking Myeloma Multicenter Group, professor of medicine at Heidelberg University Hospital in Germany, and principal investigator of the study, stated in a news release.

“These data provide evidence that the Isa-[VRd] 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,” Goldschmidt added.

Notably, previously reported data from the phase 3 IMROZ trial (NCT03319667) showed that Isa-VRd significantly reduced the risk of progression or death compared with VRd alone in patients with transplant-ineligible, newly diagnosed multiple myeloma.² Based on these findings, in May 2024, the FDA granted priority review to a supplemental biologics license application seeking the approval of Isa-VRd for the treatment of this patient population.³

GMMG HD7 was a 2-part, randomized, open-label, multicenter trial that enrolled patients 18 to 70 years of age with newly diagnosed multiple myeloma who were eligible for autologous stem cell transplant and high-dose therapy. Patients were required to have a World Health Organization performance status of 0 to 2.4 Key exclusion criteria consisted of having systemic amyloid light chain amyloidosis; plasma cell leukemia; prior chemotherapy or radiotherapy within the past 5 years, other than local radiotherapy for local myeloma progression; severe cardiac dysfunction; significant hepatic dysfunction; a history of or active hepatitis B or C; HIV positivity; and active, uncontrolled infections.

During the 2-part study, patients were first randomly assigned to receive induction therapy consisting of 10 mg/kg of isatuximab on days 1, 8, 15, 22, and 29 in cycle 1, then days 1, 15, and 29 in cycles 2 and 3, plus VRd for 3 cycles; or VRd alone. Following induction, patients were again randomly assigned to receive maintenance therapy with isatuximab plus lenalidomide or lenalidomide alone.

The rate of MRD negativity following induction and PFS after the second randomization served as the trial’s coprimary end points. Secondary end points included PFS for the different induction and maintenance combinations, overall survival, complete response rate, best response, time to second progression, safety, and quality of life.

“The GMMG HD7 study was designed to better understand the distinct effect of targeting CD38 with [isatuximab] in induction vs maintenance treatment of transplant-eligible patients,” Dietmar Berger, MD, PhD, chief medical officer and global head of development at Sanofi, added in a news release.1 “These data build upon our belief that [isatuximab] has the potential to be a best-in-class CD38 therapy that could improve long-term outcomes vs the standard of care for certain patients. We look forward to the full data presentation and continuing our mission of helping make a meaningful difference for people living with multiple myeloma.”

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://www.sanofi.com/en/media-room/press-releases/2024/2024-08-08-05-00-00-2926566
2. 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.
3. 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://www.sanofi.com/en/media-room/press-releases/2024/2024-05-27-05-00-00-2888291
4. 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 May 12, 2023. Accessed August 8, 2024. https://clinicaltrials.gov/study/NCT03617731