On March 31, 2021, the FDA accelerated the approval of a new indication for isatuximab-irfc (Sarclisa; sanofi-aventis), a CD38-directed antibody, in combination with carfilzomib and dexamethasone, for the treatment of adults with relapsed or refractory multiple myeloma who have received 1 to 3 previous lines of therapy. Isatuximab was initially approved by the FDA in 2020, in combination with pomalidomide and dexamethasone, for adults with relapsed or refractory multiple myeloma who have received ≥2 therapies, including lenalidomide and a proteasome inhibitor.
The FDA approval of isatuximab in combination with carfilzomib and dexamethasone was based on the IKEMA study, a multicenter, multinational, randomized, open-label, 2-arm, phase 3 clinical trial of patients with relapsed or refractory multiple myeloma who had received 1 to 3 lines of therapy. The study included 302 patients who were randomized in a 3:2 ratio to isatuximab plus carfilzomib and dexamethasone or to carfilzomib and dexamethasone.
The main efficacy outcome was progression-free survival (PFS). The median PFS was not reached (NR) in the isatuximab plus carfilzomib and dexamethasone arm versus 20.27 months (95% confidence interval, 15.77-NR) with carfilzomib and dexamethasone alone (P = .003), a 45% risk reduction of disease progression or death with the addition of isatuximab.
The most common (≥20%) adverse reactions with the isatuximab-based combination were upper respiratory tract infection, infusion-related reactions, fatigue, hypertension, diarrhea, pneumonia, dyspnea, insomnia, bronchitis, cough, and back pain. The most common (≥80%) hematology laboratory abnormalities were decreased hemoglobin, decreased lymphocytes, and decreased platelets.