On March 2, 2020, the FDA approved isatuximab-irfc (Sarclisa; Sanofi-Aventis), a CD38-directed cytolytic antibody, for the treatment of adults with multiple myeloma, for use in combination with pomalidomide (Pomalyst) and dexamethasone, in patients who had received at least 2 therapies that include lenalidomide (Revlimid) and a proteasome inhibitor. The FDA granted isatuximab an orphan drug designation.
“Targeting cells has led to the development of important oncology treatments. While there is no cure for multiple myeloma, Sarclisa is now another CD38-directed treatment option added to the list of FDA-approved treatments of patients with multiple myeloma who have progressive disease after previous therapies,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence. “In the clinical trial, there was a 40% reduction in the risk of disease progression or death with this therapy,” he said.
According to the National Cancer Institute, an estimated 32,270 new cases of multiple myeloma will be diagnosed in the United States in 2020 and 12,830 people will die of the disease. Although many new treatments were approved by the FDA for multiple myeloma in the past decade, the disease often relapses or becomes refractory to a specific therapy.
The FDA approval of isatuximab was based on a multicenter, multinational, randomized, open-label, 2-arm, phase 3 clinical trial that included 307 patients with relapsed or refractory multiple myeloma. All patients had received 2 or more previous therapies, which included lenalidomide and a proteasome inhibitor. The patients were randomized in a 1:1 ratio to the 3-drug combination of isatuximab plus pomalidomide and low-dose dexamethasone or to the 2 drug combination of pomalidomide plus low-dose dexamethasone.
The primary end point was progression-free survival (PFS). The improved PFS with the isatuximab-based regimen included a 40% risk reduction in disease progression or death versus the patients who received pomalidomide and low-dose dexamethasone alone (hazard ratio, 0.596; 95% confidence interval [CI], 0.44-0.81; P = .001). The median PFS with the 3-drug regimen with isatuximab was 11.53 months (95% CI, 8.94-13.9) versus 6.47 months with the 2-drug combination (95% CI, 4.47-8.28), respectively. The overall response rates were 60.4% and 35.5%, respectively.
The most common (≥20%) adverse reactions were neutropenia, infusion-related reactions, pneumonia, upper respiratory tract infection, and diarrhea. In patients with grade 3 or 4 side effects, including infusion-related reactions, isatuximab should be permanently discontinued.
The recommended dose of isatuximab is 10 mg/kg, administered as an intravenous infusion every week for 4 weeks, then every 2 weeks in combination with pomalidomide and dexamethasone, until disease progression or unacceptable toxicity.