Isatuximab Combo Earns Chinese Approval in R/R Multiple Myeloma

Supporting data for the approval came from the phase 3 ICARIA-MM trial (NCT02990338) as well as the real-world IsaFiRsT study.

China’s National Medical Products Administration (NMPA) has approved isatuximab-irfc (Sarclisa) plus pomalidomide (Pomalyst) and dexamethasone for adults with multiple myeloma who were previously treated with at least 1 therapy including lenalidomide (Revlimid) and a proteasome inhibitor, according to a press release from the developer, Sanofi.¹

Beyond this approval, the Chinese Society of Clinical Oncology and Chinese Anti-Cancer Association guidelines list the isatuximab combination as a “Category I Recommendation” and a “Preferred Option” for treating those with multiple myeloma following a first relapse. Health authorities in China are also reviewing a regulatory submission for isatuximab plus bortezomib (Velcade), lenalidomide, and dexamethasone for adults with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem cell transplant; a final decision for this indication is anticipated in the coming months.

Supporting data for the approval came from the phase 3 ICARIA-MM trial (NCT02990338) as well as the real-world IsaFiRsT study. In ICARIA-MM, combining isatuximab with pomalidomide and dexamethasone produced a 40% reduction in the risk of disease progression or death vs pomalidomide/dexamethasone alone (HR, 0.596; 95% CI, 0.44-0.81; P = .001). Additionally, isatuximab-based treatment prolonged overall survival (OS) by 6.9 months (HR, 0.78; P = .0319).

Real-world data from the IsaFiRsT study showed an overall response rate (ORR) of 82.6% with isatuximab plus pomalidomide/dexamethasone among patients with relapsed/refractory multiple myeloma in China.

“This approval marks an important milestone for [isatuximab] in China. The results of the ICARIA-MM phase 3 study, coupled with the real-world IsaFiRsT study, highlight the benefit of [isatuximab] for patients living with multiple myeloma and the importance of innovative regulatory pathways for timely access to different treatments,” Olivier Nataf, global head of Oncology at Sanofi, stated in the press release.¹ We look forward to continuing to build strong partnerships with the medical community, local companies, and authorities in China as we work to bring more innovative treatments to patients.

ICARIA-MM

Investigators of the open-label, multi-center phase 3 ICARIA-MM trial assessed treatment with isatuximab plus pomalidomide/dexamethasone vs pomalidomide/dexamethasone alone among 307 patients with relapsed/refractory multiple myeloma across 96 centers in 24 countries. Patients received isatuximab at 10 mg/kg intravenously once weekly for 4 weeks followed by every other week in 28-day cycles plus standard pomalidomide/dexamethasone.

The trial’s primary end point was progression-free survival (PFS). Secondary end points included ORR, clinical benefit rate, OS, time to progression, time to first response, pharmacokinetics, and safety.²

Patients 18 years and older with documented multiple myeloma with evidence of measurable disease, at least 2 prior lines of therapy including lenalidomide plus a proteasome inhibitor, and disease progression on or within 60 days of finishing the last prior line of therapy were eligible for enrollment on the trial. Those enrolled on the ICARIA-MM study had a median of 3 prior lines of treatment for multiple myeloma.

IsaFiRsT

The single-arm, observational, prospective, real-world IsaFiRsT study assessed 24 patients with relapsed/refractory multiple myeloma who received treatment with isatuximab plus pomalidomide/dexamethasone at a single site in China. Patients had a median of 3 prior lines of treatment, which included lenalidomide plus a proteasome inhibitor.

Investigators administered isatuximab at 10 mg/kg intravenously once weekly for 4 weeks followed by every other week in 28-day cycles in combination with standard pomalidomide/dexamethasone.

The study’s primary end point was ORR. Key secondary end points were PFS, OS, duration of response, and safety.

The FDA previously approved isatuximab plus bortezomib, lenalidomide, and dexamethasone for patients with transplant-ineligible NDMM in September 2024 based on data from the phase 3 IMROZ trial (NCT03319667).³

References

1. Sarclisa obtains first approval in China for the treatment of adult patients with relapsed or refractory multiple myeloma. News release. Sanofi. January 13, 2025. Accessed January 16, 2025. https://tinyurl.com/5xnffr9x
2. Multinational clinical study comparing isatuximab, pomalidomide, and dexamethasone to pomalidomide and dexamethasone in refractory or relapsed and refractory multiple myeloma patients (ICARIA-MM). ClinicalTrials.gov. Updated November 18, 2023. Accessed January 16, 2025. https://tinyurl.com/3ddcwn82
3. FDA approves istauximab-irfc with bortezomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma. FDA. News release. September 20, 2024. Accessed January 16, 2025. https://shorturl.at/B8d3c