The U.S. Food and Drug Administration approved Sarclisa® (isatuximab-irfc) in combination with pomalidomide and dexamethasone for adults with multiple myeloma (MM) who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.
Isatuximab-irfc is a CD38-directed cytolytic antibody that is administered through intravenous (IV) infusion.
The approval was based on results from the randomized, phase III ICARIA-MM trial that included 307 patients with relapsed/refractory MM who had received at least two prior therapies, including lenalidomide and a proteasome inhibitor. Half of the patients received isatuximab-irfc in combination with pomalidomide and low-dose dexamethasone and the other half received pomalidomide and low-dose dexamethasone alone.
Improved response, survival with isatuximab-irfc
Patients who received isatuximab-irfc in combination with pomalidomide and low-dose dexamethasone had improved progression-free survival (PFS), with a 40% reduction in the risk of disease progression or death compared with those who received pomalidomide and dexamethasone. Patients who received isatuximab-irfc had an overall response rate (ORR) of 60.4%, while patients in the pomalidomide and low-dose dexamethasone group an ORR of 35.3% (P<0.0001).
Median PFS was 11.5 months in the isatuximab-irfc group and 6.5 months in the pomalidomide and low-dose dexamethasone alone group (hazard ratio, 0.59; 95% CI, 0.44-0.81). Median treatment duration was 41 weeks and 24 weeks, respectively.
Common adverse events (AEs) associated with isatuximab-irfc were neutropenia, infusion-related reactions, pneumonia, upper respiratory tract infection, diarrhea, anemia, lymphopenia, and thrombocytopenia. Isatuximab-irfc can cause serious AEs, including IV infusion-related reactions, neutropenia, and second primary malignancies.
A smaller proportion of patients who received the isatuximab-irfc regimen discontinued treatment due to AEs (7.2% vs. 12.8%) or died of AEs (7.9% vs. 9.4%).