On March 31, 2021, the anti-CD38 monoclonal antibody isatuximab-irfc was approved for use in combination with carfilzomib and dexamethasone for the treatment of adults with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy.1
Supporting Efficacy Data
Approval was based on findings in the phase III IKEMA trial (ClinicalTrials.gov identifier NCT03275285). In the trial, 302 patients were randomly assigned 3:2 to receive 28-day cycles of isatuximab with carfilzomib and dexamethasone (Isa-Kd; n = 179) or carfilzomib and dexamethasone (Kd; n = 123); treatment continued until disease progression or unacceptable toxicity. Isatuximab at 10 mg/kg was given via intravenous (IV) infusion weekly in the first cycle and every 2 weeks thereafter. Carfilzomib and dexamethasone regimens were the same in both groups.
Isatuximab has warnings/precautions for infusion-related reactions, neutropenia, second primary malignancies, interference with laboratory tests, and embryofetal toxicity.
Independent response committee-assessed median progression-free survival at prespecified interim analysis was not reached (95% confidence interval [CI] = not reached to not reached) in the Isa-Kd group vs 20 months (95% CI = 16 months to not reached) in the Kd group (hazard ratio = 0.5, 95% CI = 0.366–0.822, P = .0032).
How It Is Used
The recommended dose in combination with carfilzomib and dexamethasone is 10 mg/kg via IV infusion on days 1, 8, 15, and 22 of the first 28-day cycle and on days 1 and 15 of all subsequent 28-day cycles, with treatment continued until disease progression or unacceptable toxicity. Dosing of carfilzomib and dexamethasone is shown in product labeling.
Isatuximab should be administered by a health-care professional with access to emergency equipment and medical support to manage infusion-related reactions. Patients should be premedicated before isatuximab infusion. No dose reductions are recommended; dose delay may be required to allow blood cell count recovery in cases of hematologic toxicity
In the IKEMA trial, the most common adverse events of any grade in the Isa-Kd group were upper respiratory tract infection (67% vs 57% in Kd group), infusion-related reactions (46% vs 3%), and fatigue (42% vs 32%). The most common grade 3 or 4 adverse events included pneumonia (22% vs 18%) and hypertension (21% vs 20%).Grade 3 or 4 hematologic abnormalities included decreased lymphocytes in 69% vs 57%, platelets in 30% vs 24%, hemoglobin in 22% vs 20%, and neutrophils in 20% vs 8%.
Serious adverse events occurred in 59% of the Isa-Kd group, most commonly pneumonia (25%). Adverse events led to discontinuation of treatment in 8%, most commonly due to infections (2.8%). Fatal adverse events occurred in 3.4% of patients (including pneumonia in 1.7% and cardiac failure in 1.1%).
Isatuximab has warnings/precautions for infusion-related reactions, neutropenia, second primary malignancies, interference with laboratory tests, and embryofetal toxicity. Isatuximab is contraindicated in patients with severe hypersensitivity to isatuximab or to any of its excipients.
1. Sarclisa (isatuximab-irfc) injection prescribing information, sanofi-aventis US LLC, March 2021. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761113s003lbl.pdf. Accessed May 3, 2021.