Use of Sirolimus in GLA/GSD/KLA

Presented by Cameron Trenor, MD, MMSc, Vascular Anomaly Center, Boston Children’s Hospital

Sirolimus has been FDA-approved since 1999 for immunosuppression but has many appreciated off-label uses, including for lymphatic disorders. Based on clinical study results and reported cases, sirolimus is often used for Gorham-Stout disease (GSD), generalized lymphatic anomaly (GLA)/lymphangiomatosis and other lymphatic conditions. Many lymphatic malformations are associated with activating somatic mutations in PIK3CA, for which it is logical to treat with an mTOR inhibitor, such as sirolimus. The genetics and biology of GSD and GLA are still only partially understood, though new discoveries of PIK3CA and NRAS mutations have been reported. There is no known effect of diet on disease, except that fat intake can increase lymphatic (especially chylous) leak volume. Related to sirolimus therapy, fat intake may be lowered to assist in cholesterol control and grapefruit should be avoided. Our current approach to medical therapies for these disorders in to treat certain complications, rather than the genetics or disease entity itself. Pleural effusions, bone disease, soft tissue lesions and other areas of lymphatic leak may respond to sirolimus. It is important to agree upon goals of therapy and how to measure response before starting. Close follow-up including laboratory follow-up is necessary to delivery sirolimus therapy safely. We will review known side effects in this talk, all of which are dose-related and reversible. Sirolimus is well-tolerated by the majority of patients. The future of medical therapy for GSD and GLA is likely to involve combination therapies and novel drugs targeting genetic and biologic discoveries.

About the Presenter

Pediatric Hematology/Oncology
Vascular Anomalies Center Boston Children’s Hospital Director
Senior TME 1 Novartis Institutes of BioMedical Institute

Dr. Trenor is a hematologist/oncologist at Boston Children’s Hospital where he has been  involved with the Vascular Anomalies Center since 2010 and has co-authored several important papers about vascular anomalies. In 2018 he joined Novartis Institutes for BioMedical Research (NIBR) where he is provides hematology expertise to first-in-human and proof-of-concept trials in hematologic diseases, rare diseases and pediatric studies, including small molecules, biologics and gene therapy technologies.

In 2016 Dr. Trenor was awarded  the LGDA Founder’s Award.

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