Sarclisa Combination Shows Positive Results in Patients With Relapsed Multiple Myeloma

Latest results of the phase 3 IKEMA trial demonstrate the longest median progression-free survival on a proteasome inhibitor backbone in this population, Sanofi says.

Isatuximab-irfc (Sarclisa) in combination with carfilzomib and dexamethasone demonstrated a median progression-free survival (mPFS) of 35.7 months compared with 19.2 months in individuals treated with carfilzomib and dexamethasone alone in the phase 3 IKEMA clinical trial, Sanofi said in a statement.

An independent review committee evaluated the study, and the results were presented at the Controversies in Multiple Myeloma World Congress. The data will also be presented at the European Society for Medical Oncology.

Additionally, the study represented the longest mPFS among studies that investigated a proteasome inhibitor backbone in the second-line setting for the treatment of relapsed multiple myeloma.

“The increase in PFS, observed consistently across all subgroups, when adding [isatuximab-irfc] to carfilzomib and dexamethasone is remarkable in patients with relapsed multiple myeloma in a proteasome inhibitor combination. Relapse is common in multiple myeloma, creating the need for differentiated second-line treatments that provide patients a longer period of time without disease progression,” Philippe Moreau, MD, head of the Department of Hematology at the University Hospital of Nantes in France, said in the statement.

“This updated analysis reinforces the potential for [isatuximab-irfc] to become a new standard of care for patients with relapsed multiple myeloma,” he said.

A PFS analysis following the FDA recommendation on censoring rules, as applied in the approved United States prescribing information, showed an mPFS of 41.7 months for isatuximab-irfc added to carfilzomib and dexamethasone compared with 20.8 months in individuals treated with carfilzomib and dexamethasone alone.

Time to next treatment for individuals treated with the combination therapy was 44.9 months versus those treated with carfilzomib and dexamethasone alone at 25 months. Investigators defined time to next treatment as the interval for the date of randomization to the date of commencement of the next line of therapy, allowing for measurements of the period of therapeutic benefit.

“To observe progression-free survival of more than 3 years in patients with relapsed multiple myeloma when [isatuximab-irfc] was added to a proteasome inhibitor backbone of therapy is unprecedented and reinforces our confidence in [isatuximab-irfc] as a potential best in class anti-CD38 antibody,” Peter Adamson, MD, global head of Oncology Clinical Development and Pediatric Innovation at Sanofi, said in the statement.

The safety and tolerability of isatuximab-irfc observed in the analysis were consistent with the safety profile of isatuximab-irfc in other clinical trials, with no new safety signals observed.

For the combination therapy and carfilzomib with dexamethasone, the most common adverse events (AEs) were back pain at 25.4% and 21.3%, bronchitis at 24.3% and 12.3%, diarrhea at 29.5% and 32%, dyspnea at 30.5% and 22.1%, fatigue at 31.6% and 20.5%, hypertension at 37.9% and 35.2%, infusion-related reaction at 45% and 3%, insomnia at 25.4% and 24.6%, pneumonia at 27.1% and 21.3%, and upper-respiratory-tract infection at 37.3% and 27%, respectively.

Additionally, treatment exposure in the combination arm was 30 weeks longer than in the control arm. Treatment-emergent AEs of greater than or equal to grade 3 were reported in 83.6% of individuals treated with the combination therapy and in 73% of individuals treated with carfilzomib and dexamethasone alone. Serious treatment emergent AEs were higher in the combination therapy arm at 70.1% compared with carfilzomib and dexamethasone alone at 59.8%.

No differences were observed after exposure adjustment.

Reference

Sarclisa (isatuximab-irfc) combination provides unprecedented median progression free survival in patients with relapsed multiple myeloma receiving a proteasome inhibitor therapy. Sanofi. News release. May 15, 2022. Accessed May 17, 2022. https://www.news.sanofi.us/2022-05-15-Sarclisa-R-isatuximab-irfc-combination-provides-unprecedented-median-progression-free-survival-in-patients-with-relapsed-multiple-myeloma-receiving-a-proteasome-inhibitor-therapy