Long-term outcomes of sirolimus treatment for kaposiform hemangioendothelioma: Continuing successes and ongoing challenges

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.

Automated summary

Sirolimus treatment has shown improved prognosis in patients with kaposiform hemangioendothelioma (KHE), but the long-term efficacy and tolerability have not been well elucidated. This study found that 92.2% of patients had a durable response to sirolimus treatment, but rebound growth occurred in some patients upon discontinuation. Although long-term treatment with sirolimus was not associated with unacceptable toxicities, challenges remain in nonresponse, tumor relapse, and long-term sequelae.