Is sirolimus a therapeutic option for patients with progressive pulmonary lymphangioleiomyomatosis?

Abstract

BackgroundLymphangioleiomyomatosis (LAM) is a rare lung disease characterised by progressive airflow obstruction. No effective medical treatment is available but therapy with sirolimus has shown some promise. The aim of this observational study was to evaluate sirolimus in progressive LAM.MethodsSirolimus (trough level 5 - 10 ng/ml) was administered to ten female patients (42.4 ± 11.9 years) with documented progression. Serial pulmonary function tests and six-minute-walk-distance (6-MWD) assessments were performed.ResultsThe mean loss of FEV1 was -2.30 ± 0.52 ml/day before therapy and a significant mean gain of FEV1 of 1.19 ± 0.26 ml/day was detected during treatment (p = 0.001). Mean FEV1 and FVC at baseline were 1.12 ± 0.15 l (36.1 ± 4.5%pred.) and 2.47 ± 0.25 l (69.2 ± 6.5%pred.), respectively. At three and six months during follow-up a significant increase of FEV1 and FVC was demonstrated (3 months ΔFEV1: 220 ± 82 ml, p = 0.024; 6 months ΔFEV1: 345 ± 58 ml, p = 0.001); (3 months ΔFVC: 360 ± 141 ml, p = 0.031; 6 months ΔFVC: 488 ± 138 ml, p = 0.006). Sirolimus was discontinued in 3 patients because of serious recurrent lower respiratory tract infection or sirolimus-induced pneumonitis. No deaths and no pneumothoraces occurred during therapy.ConclusionsOur data suggest that sirolimus might be considered as a therapeutic option in rapidly declining LAM patients. However, sirolimus administration may be associated with severe respiratory adverse events requiring treatment cessation in some patients. Moreover, discontinuation of sirolimus is mandatory prior to lung transplantation.

Lymphangioleiomyomatosis: New Concepts in Pathogenesis, Diagnosis, and Treatment

“…110 A German study of patients referred for lung transplantation showed reversal of rapidly declining lung function in 10 subjects who had a mean improvement in FEV 1 of 345 AE 58 mL after 6 months on therapy. 113 Three patients discontinued use of the drug due to side effects, however.…”

Optimizing treatments for lymphangioleiomyomatosis

“…An off-label study undertaken in ten patients with severe LAM treated with sirolimus showed a significant improvement in FVC and FEV 1 after 3 and 6 months of therapy [77]. …”

LAM: Neue Therapien – neue Chancen?

“…Dieser "Landmark"-Studie folgten weitere, nicht plazebokontrollierte Studien, die den Effekt von Sirolimus bestätigten [7] und zudem eine Reduktion der zirkulierenden LAM-Zellen unter Sirolimus [8] sowie die Reduktion eines Chylothorax aufzeigen konnten. Sirolimus ist offenbar auch in einer niedrigeAbb.…”