Treatment of Lymphatic Malformations with the mTOR Inhibitor Sirolimus: A Systematic Review

Abstract

Available literature indicated that sirolimus therapy might be effective for lymphatic malformations. However, further randomized controlled studies are required to analyze the efficacy and long-term adverse events and to clarify the potential role for sirolimus in the management of lymphatic malformations.

Efficacy of systemic sirolimus in the treatment of generalized lymphatic anomaly and Gorham–Stout disease

“…9 Although prospective clinical trials have been limited, numerous reports have been published on the efficacy of sirolimus treatment for LM as well as combined malformations with a lymphatic component. [9][10][11][12][13][14][15][16] This evidence, along with the identification of germline and somatic mutations within the PI3K/Akt/mTOR and associated pathways in lymphatic disorders, supports the use of sirolimus for treatment of complex LM and associated complications.…”

“…The prospective phase 2 clinical trial (NCT00975819) by Adams et al demonstrated that sirolimus was well‐tolerated and efficacious in the treatment of multiple complicated vascular anomalies . Although prospective clinical trials have been limited, numerous reports have been published on the efficacy of sirolimus treatment for LM as well as combined malformations with a lymphatic component . This evidence, along with the identification of germline and somatic mutations within the PI3K/Akt/mTOR and associated pathways in lymphatic disorders, supports the use of sirolimus for treatment of complex LM and associated complications.…”

Treatment of superficial vascular anomalies with topical sirolimus: A multicenter case series

“…Sirolimus, an mTOR inhibitor, is an evolving therapy for vascular anomalies with promising results. Several studies have demonstrated the efficacy of systemic sirolimus in the treatment of complicated vascular anomalies mainly by not only reducing the size and associated complications but also reducing frequency of infections and improving coagulopathies when present . Systemic sirolimus is generally tolerated well, with the most common side effects being hyperlipidemia and neutropenia …”

“…Several studies have demonstrated the efficacy of systemic sirolimus in the treatment of complicated vascular anomalies mainly by not only reducing the size and associated complications but also reducing frequency of infections and improving coagulopathies when present. 5,6 Systemic sirolimus is generally tolerated well, with the most common side effects being hyperlipidemia and neutropenia. 5,6 Topical sirolimus has most commonly been used to treat angiofibromas associated with tuberous sclerosis, and in this population, it is proved to be effective and well-tolerated.…”

“…5,6 Systemic sirolimus is generally tolerated well, with the most common side effects being hyperlipidemia and neutropenia. 5,6 Topical sirolimus has most commonly been used to treat angiofibromas associated with tuberous sclerosis, and in this population, it is proved to be effective and well-tolerated. In a randomized control trial of adults and children, the maximum systemic absorption was less than 0.25 ng/mL, which is 20-to 60-fold less than systemic levels seen with oral administration.…”