Efficacy and safety of oral sirolimus for high‐flow vascular malformations in real clinical practice

Abstract

Background. Vascular malformations are a complex pathology with few treatment options. In previously published studies, oral sirolimus (rapamycin) has shown promising results in the treatment of low-flow vascular malformations, but its usefulness in high-flow vascular malformations is controversial. Aim. To evaluate the efficacy and safety of sirolimus for the treatment of high-flow vascular malformations in real-life practice. Methods. In a unit specializing in vascular anomalies, patients treated with oral sirolimus for high-flow vascular malformations were located by consulting the drug dispensations. Reviewing the electronic medical records, data on patient demographics, vascular malformation characteristics, treatments, toxicity and clinical course were collected and statistically analysed. Results. Nine patients with vascular malformations were included: eight had arteriovenous malformation and one had arteriovenous fistula. Six of these malformations were isolated while three were part of a syndrome. Sirolimus was initiated at a dosage of 1-4 mg/day to be taken as a single dose. Partial response was observed in eight of the nine patients (88.9%) with high-flow vascular malformation, while worsening was observed in the remaining patient. The treatment was well tolerated and at the most recent follow-up, five patients remained on treatment with oral sirolimus. Conclusion. Our results show that oral sirolimus is a well-tolerated therapeutic option, with an excellent safety profile, which can be useful in the long-term stabilization of patients with high-flow vascular malformations. Single-daily dosage may improve long-term adherence to treatment without worsening its effectiveness.

Indications and Limitations of Sirolimus in the Treatment of Vascular Anomalies—Insights From a Retrospective Case Series

“…It is hypothesized that heterogeneous responses of high flow malformations to sirolimus might be related to their molecular background ( 19 ). The scarcity of molecular substrate in AVM as a target for mTOR inhibitors would result in poor response and vice versa ( 20 ). The efficacy of sirolimus in AVM is being investigated in a prospective phase II study ( 21 ).…”