Efficacy and safety of high-vs low-dose sirolimus in patients with kaposiform hemangioendothelioma: A randomized clinical trial.

Abstract

It remains unknown whether low-dose sirolimus can replace high-dose sirolimus for the treatment of kaposiform hemangioendothelioma (KHE) without the Kasabach-Merritt phenomenon. To evaluate the noninferiority and safety of low-dose versus high-dose sirolimus in KHE patients. This randomized, multicenter, open-label, noninferiority trial was conducted from February 2021 to August 2022. Participants received either a low-dose sirolimus regimen (blood trough concentration 5-8 ng/mL) or a high-dose sirolimus regimen (blood trough concentration 10-15 ng/mL). The primary endpoint was the difference in the proportion of patients between groups who achieved an objective response, defined as a ≥20% reduction in KHE volume at month 12. In this study, 39 were in the low-dose group, and 40 were in the high-dose group. At 1 year of treatment, 90.0% in the high-dose group and 89.7% in the low-dose group achieved an objective response (difference, 0.3%; 95% confidence interval -13.1 to 13.6). The incidences of total adverse events and serious adverse events were similar between the 2 groups, but respiratory, skin, and mucosal adverse events were less common in the low-dose group. The patients enrolled were not associated with Kasabach-Merritt phenomenon. Low-dose sirolimus is noninferior to high-dose sirolimus in treating KHE.