FDA approves Sarclisa-based regimen for multiple myeloma
The FDA approved isatuximab-irfc for use in combination with carfilzomib and dexamethasone for the treatment of adults with relapsed or refractory multiple myeloma who previously received one to three prior lines of therapy.
The FDA based this approval, in part, on data from the multicenter, open-label randomized phase 3 IKEMA trial, which included 302 patients randomly assigned 3:2 to receive isatuximab-irfc (Sarclisa, Sanofi-Aventis) with carfilzomib (Kyprolis, Amgen) and dexamethasone, or carfilzomib and dexamethasone alone.
PFS — assessed by an independent response committee based on central laboratory data for M-protein, as well as by central radiologic imaging review using International Myeloma Working Group criteria — served as the study’s primary endpoint.
Results showed median PFS was not reached among patients assigned the isatuximab-irfc combination, compared with 20.27 months for those assigned carfilzomib and dexamethasone alone (HR = 0.548; 95% CI, 0.366-0.822). OS data were immature at the time of the interim analysis.
Overall response rate did not differ significantly between the isatuximab-irfc combination and control groups (86.6% vs. 82.9%), with complete response rates of 39.7% vs. 27.6%.
The most common adverse events associated with the isatuximab-irfc combination included upper respiratory tract infection, infusion-related reactions, fatigue, hypertension, diarrhea, pneumonia, dyspnea, insomnia, bronchitis, cough and back pain. Hematology laboratory abnormalities that occurred among more than 80% of treated patients included decreases in hemoglobin, lymphocytes and platelets.
“In the phase 3 IKEMA study, the addition of Sarclisa to carfilzomib and dexamethasone reduced risk [for] disease progression or death by 45%,” Thomas G. Martin, MD, associate director of the myeloma program at University of California, San Francisco, and professor of medicine and the adult leukemia and bone marrow transplantation program and co-leader of the hematopoietic malignancies program at Helen Diller Family Comprehensive Cancer Center, said in a manufacturer-issued press release. “This approval is an important advancement for patients whose disease has relapsed and reinforces the potential for Sarclisa to become a standard of care in relapsed or refractory multiple myeloma.”
Isatuximab-irfc also is approved in the U.S. in combination with pomalidomide (Pomalyst, Bristol Myers Squibb) and dexamethasone for adults with relapsed/refractory multiple myeloma who have received at least two prior therapies, including lenalidomide (Revlimid, Celgene) and a proteasome inhibitor.