The FDA has approved isatuximab-irfc (Sarclisa®, Sanofi) in combination with carfilzomib and dexamethasone (Kd), for adult patients with relapsed or refractory multiple myeloma who have previously received one to three lines of therapy.
"Treatment of relapsed/refractory multiple myeloma (RRMM) has greatly improved, yet relapse is inevitable and additional effective treatments are needed," wrote Philippe Moreau, MD, Head of the Hematology Department at the University Hospital of Nantes in France, and colleagues, in the interim analysis of the phase 3 IKEMA trial (NCT03275285), on which the approval was based.
The trial evaluated the safety and efficacy of isatuximab-irfc/Kd in 302 patients with relapsed and/or refractory multiple myeloma who had received one to three prior lines of therapy. Of the 302 patients, 179 were treated with isatuximab-irfc in combination with Kd, while 123 patients were treated with Kd only. The primary end point was progression-free survival, with secondary end points of overall response rate, complete response rate, very good partial response rate, minimal residual disease negativity, and overall survival.
At a median follow-up of 20.7 months, isatuximab-irfc/Kd produced higher rates of overall response (86.6% vs 82.9%), very good partial response (72.6% vs 56.1%), complete response (39.7% vs 27.6%), and minimal residual disease negativity (29.6% vs 13.0%) compared with Kd alone. Median overall survival had not been reached. At the time of the approval, median progression-free survival was not reached for patients who had been treated with isatuximab-irfc/Kd compared with 20.27 months in the Kd–only arm. There was a 45% reduction in the risk of disease progression or death in patients treated with isatuximab-irfc/Kd compared with those treated with Kd alone.
The most common adverse events occurring in at least 20% of patients receiving isatuximab-irfc/Kd included upper respiratory tract infection, infusion-related reactions, fatigue, hypertension, diarrhea, pneumonia, dyspnea, insomnia, bronchitis, cough, and back pain. The most common laboratory abnormalities occurring in at least 80% of patients included decreased hemoglobin, decreased lymphocytes, and decreased platelets.
"The addition of isatuximab to Kd provided a superior, statistically significant improvement in progression-free survival with clinically meaningful improvement in depth of response," concluded Dr. Moreau and colleagues in their abstract presented at the American Society of Hematology Annual Meeting in December 2020. "Isatuximab/Kd was well tolerated with manageable safety and a favorable benefit-risk profile, and represents a possible new standard-of-care treatment in patients with relapsed multiple myeloma."
The recommended dose of isatuximab-irfc in combination 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.
For More Information
Moreau P, Dimopoulos MA, Mikhael J, et al (2020). Isatuximab plus carfilzomib and dexamethasone vs carfilzomib and dexamethasone in relapsed/refractory multiple myeloma (IKEMA): interim analysis of a phase 3, randomized, open-label study. Blood (ASH Annual Meeting Abstracts). Abstract 2316.
Clinicaltrials.gov (2021). Multinational clinical study comparing isatuximab, carfilzomib and dexamethasone to carfilzomib and dexamethasone in relapse and/or refractory multiple myeloma patients (IKEMA). NLM identifier: NCT03275285.
US Food & Drug Administration (2021). FDA approves isatuximab-irfc for multiple myeloma. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-isatuximab-irfc-multiple-myeloma
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