Treatment with
sirolimus, an inhibitor of the
mammalian target of rapamycin pathway, has improved the prognosis of patients with
kaposiform hemangioendothelioma (KHE). However, the efficacy, durability and tolerability of long-term
sirolimus treatment in patients with KHE have not been well elucidated. We performed efficacy and safety assessments based on more than 4.5 years of follow-up in patients receiving
sirolimus therapy for KHE. One hundred sixty-seven patients were analyzed, including 102 (61.1%) patients with the
Kasabach-Merritt phenomenon (KMP). Follow-up was conducted after a median of 56.0 months. A total of 154 (92.2%) patients had a durable response to
sirolimus treatment. No difference in durable response was found between patients without KMP and patients with KMP (95.4% vs 90.2%; difference, 5.2%; 95% confidence interval [CI], -4.0% to 13.1%). Rebound growth occurred in 17.3% of patients upon
sirolimus discontinuation. Early treatment discontinuation (odds ratio [OR]: 3.103; 95% CI: 1.529-6.299; P = .002) and mixed lesion type (OR: 2.271; 95% CI: 0.901-5.727; P = .047) were associated with
tumor rebound growth. No KHE-related deaths occurred in this cohort. At the last follow-up, approximately 17.4% of patients had active disease and/or changes in body structures to a variable extent. Serious adverse events occurred most commonly during the first year of
sirolimus therapy. Follow-up of almost 4.5 years demonstrated that the efficacy of
sirolimus persisted over time and that long-term treatment with
sirolimus was not associated with unacceptable cumulative toxicities. However, nonresponse,
tumor relapse and long-term sequelae remained challenges despite intensified and prolonged
sirolimus therapy.