On March 31, the U.S. Food and Drug Administration (FDA) approved isatuximab-irfc (Sarclisa) in combination with carfilzomib and dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy.
The efficacy and safety of isatuximab in combination with carfilzomib and dexamethasone was evaluated in IKEMA (ClinicalTrials.gov identifier NCT03275285), a multicenter, multinational, randomized, open-label, two-arm, phase III trial that enrolled patients with relapsed and/or refractory multiple myeloma who had received one to three prior lines of therapy. The trial randomly assigned 302 patients 3:2 to receive isatuximab with carfilzomib and dexamethasone or carfilzomib and dexamethasone (Kd).
The main efficacy outcome measure was progression-free survival, assessed by an independent response committee based on central laboratory data for M-protein and central radiologic imaging review using International Myeloma Working Group criteria. Median progression-free survival was not reached in the isatuximab plus carfilzomib and dexamethasone arm and was 20.27 months (95% confidence interval [CI] = 15.77–not reached) in the carfilzomib plus dexamethasone arm (hazard ratio = 0.548, 95% CI = 0.366–0.822, P = .0032), representing a 45% reduction in the risk of disease progression or death in patients treated with isatuximab plus carfilzomib and dexamethasone compared to those treated with carfilzomib plus dexamethasone.
The most common adverse reactions (≥ 20%) in patients receiving isatuximab plus carfilzomib and dexamethasone were upper respiratory tract infection, infusion-related reactions, fatigue, hypertension, diarrhea, pneumonia, dyspnea, insomnia, bronchitis, cough, and back pain. The most common hematology laboratory abnormalities (≥ 80%) were decreased hemoglobin, decreased lymphocytes, and decreased platelets.
The recommended isatuximab dose with carfilzomib and dexamethasone is 10 mg/kg as an intravenous infusion every week for 4 weeks followed by every 2 weeks until disease progression or unacceptable toxicity.