What question did this study set out to answer?

This study aims to evaluate the long-term effectiveness and safety of sirolimus therapy in patients with lymphangioleiomyomatosis.

June 15, 2026Open Access

Long-term outcomes of sirolimus therapy in sporadic and tuberous sclerosis complex–associated lymphangioleiomyomatosis: a retrospective cohort study

Key Points

This study aims to evaluate the long-term effectiveness and safety of sirolimus therapy in patients with lymphangioleiomyomatosis.
Retrospective analysis of adults with LAM treated with sirolimus from 2010 to 2020 at a national center in Poland.
Seventy-one patients included, with median follow-up of 5 years and analysis of pulmonary and lymphatic outcomes.
FEV1 improved by a median of 0.03 L at 12 months (n=66; P=0.03).
Chylous effusions resolved in all 15 affected patients within 12 months without recurrence.
VEGF-D decreased during treatment and was associated with lymphatic involvement.

Abstract

INTRODUCTION: Sirolimus is the standard disease-modifying therapy for lymphangioleiomyomatosis (LAM), but long-term routine-care data integrating pulmonary, lymphatic, extrapulmonary, and biomarker outcomes remain limited. OBJECTIVES: To assess long-term effectiveness and safety of sirolimus in routine clinical practice. PATIENTS AND METHODS: We retrospectively analyzed consecutive adults with definite LAM treated with sirolimus at a national tertiary referral center in Poland between 2010 and 2020. RESULTS: Seventy-one patients were included (70 women; 57/71 80% with sporadic LAM and 14/71 20% with TSC-associated disease). The median duration of available functional follow-up was 5.0 years IQR, 2.0-5.0, and mean trough sirolimus concentration was 7.85 (2.36) ng/mL. Baseline chylous pleural and/or peritoneal effusions were present in 15/71 (21%), renal angiomyolipomas in 33/71 (46%), and lymphangioleiomyomas in 28/71 (39%) patients. FEV1 increased at 12 months by a median Δ of 0.03 L IQR, -0.10 to 0.30 from baseline (n=66; P=0.03). FVC and 6-minute walk distance also improved during early follow-up, while TLCO remained generally stable. Chylous effusions resolved in all affected patients by 12 months without recurrence, and renal angiomyolipoma and lymphangioleiomyoma volumes decreased significantly in patients with paired MRI measurements. Higher baseline VEGF-D was associated with lymphatic involvement, and VEGF-D decreased during treatment. Adverse events were mostly mild; permanent discontinuation occurred in approximately 6%. CONCLUSIONS: In routine practice, sirolimus was associated with long-term stabilization of lung function, marked improvement of lymphatic disease, reduction of angiomyolipoma burden, and acceptable tolerability. VEGF-D aligned with lymphatic phenotype and declined with treatment, supporting its role as a monitoring biomarker.

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