Isatuximab Plus Pomalidomide and Dexamethasone Receives Approval in China for Relapsed/Refractory Multiple Myeloma

The Chinese National Medical Products Administration (NMPA) has approved isatuximab-irfc (Sarclisa) plus pomalidomide (Pomalyst) and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least 1 prior line of treatment, including lenalidomide (Revlimid) and a proteasome inhibitor.1

The regulatory decision is supported by findings from the pivotal phase 3 ICARIA-MMtrial (NCT02990338) using the China-based IsaFiRsT real-world study as bridging data. At a median follow-up of 52.4 months, patients who received isatuximab in combination with pomalidomide and dexamethasone (n = 154) achieved a median investigator-assessed progression-free survival (PFS) of 11.1 months (95% CI, 7.8-13.8) compared with 5.9 months (95% CI, 4.5-7.9) among those who received only pomalidomide and dexamethasone (n = 153; HR, 0.57; 95% CI, 0.44-0.73; 1-sided P < .0001).2 The median overall survival (OS) was 24.6 months (95% CI, 20.3-31.3) vs 17.7 months (95% CI, 14.4-26.2), respectively (HR, 0.78; 95% CI, 0.59-1.02; 1-sided P = .0319).

“This approval marks an important milestone for Sanofi in China,”Olivier Nataf, MS, global head of oncology, Sanofi, stated in a news release.1 “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. 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.”

Isatuximab is a CD38-directed monoclonal antibody that is designed to bind to a specific epitope on the CD38 receptor of multiple myeloma cells. The agent induces antitumor activity via multiple mechanisms of action, including apoptosis and immunomodulatory activity.

ICARIA-MM was a multicenter, open-label study that enrolled adult patients with relapsed/refractory multiple myeloma who had received at least 2 prior therapies and failed treatment with lenalidomide and a proteasome inhibitor, alone or as a combination component.2 Patients who were refractory to prior anti-CD38 therapy, had previous pomalidomide exposure, an ECOG performance status above 2, an ongoing toxic effect above grade 2 from previous treatment, had active primary amyloid light-chain amyloidosis, or had concomitant plasma cell leukemia were excluded from the study.

Eligible patients were randomly assigned 1:1 to the investigational or control arm. In the investigational arm, patients received intravenous (IV) isatuximab at a dose of 10 mg/kg on days 1, 8, 15, and 22 of cycle 1 and days 1 and 15 for subsequent cycles in combination with IV or oral dexamethasone at a dose of 40 mg (20 mg if age ≥ 75 years) on days 1, 8, 15, and 22, and oral pomalidomide at a dose of 4 mg on days 1 to 21. Patients in the control arm received dexamethasone and pomalidomide only via the same dosing schedule as the investigational arm.

The primary end point was PFS per independent review committee. Key secondary end points included overall response rate (ORR) and OS. Median PFS on subsequent therapy or death (PFS2), ORR on further therapy, PFS on the first line of further therapy, and time to next treatment (TNNT) served as exploratory end points.

Additional data from ICARIA-MM showed that the ORR was 63% (95% CI, 55%-71%) in the investigational arm compared with 33% (95% CI, 26%-41%) in the control arm. The median PFS2 was 17.5 months (95% CI, 14.9-19.2) compared with 12.9 months (95% CI, 10.1-16.6), respectively (HR, 0.735; 95% CI, 0.569-0.950; log-rank P = .0091). The median TNNT was 15.5 months (95% CI, 12.1-19.8) vs 8.9 months (95% CI, 6.3-11.5), respectively (HR, 0.548; 95% CI, 0.417-0.718; P < .0001).

The median treatment duration in the investigational arm was 11.0 months (range, 2.6-12.4) and 5.5 months (range, 4.4-21.8) in the control arm. Safety findings demonstrated that treatment-emergent serious adverse effects were reported in 74% vs 61% of patients, respectively. Fatal treatment-emergent adverse effects (TEAEs) occurred in 15% vs 13% of patients, respectively. The most common any-grade TEAEs in both arms included neutropenia (52% vs 36%), infusion-related reactions (37.5% vs 1%), and upper respiratory infection (36% vs 21%).

Beyond the approval by the NMPA, the Chinese Society of Clinical Oncology and Chinese Anti-Cancer Association guidelines include isatuximab plus pomalidomide and dexamethasone as a category 1 recommendation and the preferred option for the treatment of patients with multiple myeloma at first relapse.1 A regulatory submission for isatuximab plus bortezomib (Velcade), lenalidomide, and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant is also under review in China with a final decision expected in the coming months.

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 13, 2025. https://www.globenewswire.com/news-release/2025/01/13/3008102/0/en/Press-Release-Sarclisa-obtains-first-approval-in-China-for-the-treatment-of-adult-patients-with-relapsed-or-refractory-multiple-myeloma.html
2. Richardson PG, Perrot A, Miguel JS, et al. Isatuximab-pomalidomide-dexamethasone versus pomalidomide-dexamethasone in patients with relapsed and refractory multiple myeloma: final overall survival analysis. Haematologica. 2024;109(7):2239-2249. doi:10.3324/haematol.2023.284325