China's NMPA Approves Isatuximab Plus VRd for Newly Diagnosed, Transplant-Ineligible Myeloma

China’s National Medical Products Administration (NMPA) has approved isatuximab (Scarlisa) in combination with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (Isa-VRd) for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT).

The approval was based on findings from the phase 3 IMROZ trial (NCT03319667), which demonstrated that Isa- VRd reduced the risk of disease progression or death by 40.4% compared with VRd alone (HR, 0.596; 98.5% CI, 0.406-0.876; P = .0005).2 Findings presented at the 2024 ASCO Annual Meeting showed that at a median follow-up of 59.7 months, the median progression-free survival (PFS) was not reached (NR) in the Isa-VRd arm vs 54.34 months (95% CI, 45.207-NR) in the VRd arm. The 60-month PFS rate was 63.2% with Isa-VRd vs 45.2% with VRd.

“When Sanofi entered China more than 4 decades ago, we did so with the intention of bringing potentially transformative therapies to Chinese patients. This approval, occurring just weeks after [isatuximab’s] first [approval] in the country, represents tremendous progress toward advancing this mission. Now, patients with multiple myeloma and their providers have access to two new [isatuximab]-based regimens that have the potential to improve outcomes across lines of therapy," Olivier Nataf, global head of Oncology at Sanofi, stated in a news release.1

In September 2024, the FDA approved Isa-VRd for adult patients with newly diagnosed multiple myeloma who are not eligible for ASCT.3 This approval was also supported by data from IMROZ.

Study Design

IMROZ was a global, randomized trial evaluating the efficacy and safety of Isa-VRd vs VRd alone in patients with newly diagnosed multiple myeloma ineligible for ASCT.2 The trial enrolled 446 patients no older than 80 years of age, and transplant ineligibility was based on age or comorbidities.

Patients were randomly assigned in a 3:2 ratio to receive Isa-VRd followed by Isa-Rd or VRd followed by Rd as continuous treatment. In the Isa-VRd arm, patients received isatuximab at 10 mg/kg IV weekly in cycle 1 and every 2 weeks in cycles 2 to 4, in addition to bortezomib at 1.3 mg/m² on days 1, 4, 8, 11, 22, 25, 29, and 32 in cycles 1 to 4, lenalidomide at 25 mg on days 1 to 14 and 22 to 35, and dexamethasone at 20 mg on days 1, 2, 4, 5, 8, 9, 11, 12, 15, 22, 23, 25, 26, 29, 30, 32, and 33 in cycles 1 to 4. In the VRd arm, patients received the same regimen without isatuximab. Following the induction phase, patients in both arms transitioned to continuous therapy with Isa-Rd or Rd until disease progression, unacceptable toxicity, or patient withdrawal. Patients in the VRd arm who experienced disease progression were permitted to cross over to receive Isa-Rd.

The primary end point of the trial was PFS. Key secondary end points included overall survival (OS), complete response (CR) rate, minimal residual disease (MRD)–negativity rate (at a 10⁻⁵ sensitivity), and very good partial response (VGPR) rate. MRD was assessed through bone marrow aspirate at predefined time points, including at the end of induction and at 12, 18, 24, and 36 months.

Response and Additional Efficacy Data

Additional efficacy findings showed that Isa-VRd produced an overall response rate (ORR) of 91.3%, including a CR or better in 74.7% of patients. These rates were 92.3% and 64.1%, respectively, in the VRd arm.

The MRD-negativity rate in the intention-to-treat population was significantly higher with Sarclisa-VRd vs VRd (58.1% vs 43.6%; odds ratio [OR], 1.791; 95% CI, 1.221-2.627; P = .003). Notably, MRD negativity was sustained for at least 12 months in 46.8% of patients in the experimental arm vs 24.3% in the control arm (OR, 2.729; 95% CI, 1.799-4.141).

Overall survival (OS) data remained immature; however, a favorable trend was observed for Isa-VRd (HR, 0.776; 95% CI, 0.407-1.48).

Isa-VRd was well tolerated, and the safety profile remained consistent with that of the individual agents.

References

1. Sarclisa is the first anti-CD38 treatment in combination with standard-of-care VRd approved in China for patients with newly diagnosed multiple myeloma ineligible for transplant. News release. Sanofi. January 31, 2025. Accessed January 31, 2025. https://www.sanofi.com/en/media-room/press-releases/2025/2025-01-31-06-00-00-3018540
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. FDA approves isatuximab-irfc with bortezomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma. FDA. September 20, 2024. Accessed January 31, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-isatuximab-irfc-bortezomib-lenalidomide-and-dexamethasone-newly-diagnosed-multiple