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

INTRODUCTION

Sirolimus is a standard disease‑modifying therapy for lymphangioleiomyomatosis (LAM), but long‑term routine‑care data integrating pulmonary, lymphatic, extrapulmonary, and biomarker outcomes remain limited.

OBJECTIVES

Our aim was to assess long‑term effectiveness and safety of sirolimus in routine clinical practice.

PATIENTS AND

METHODS

We retrospectively analyzed consecutive adult patients 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 [80%] with sporadic LAM and 14 [20%] with tuberous sclerosis complex-associated disease). Median (interquartile range) duration of available functional follow‑up was 5 (2-5) years, and mean (SD) trough sirolimus concentration was 7.85 (2.36) ng/ml. Baseline chylous pleural and / or peritoneal effusions were present in 15 patients (21%), renal angiomyolipomas in 33 (46%), and lymphangioleiomyomas in 28 individuals (39%). Forced expiratory volume in 1 second increased at 12 months by a median of 0.03 (-0.1 to 0.3) l from baseline (n = 66; P = 0.03). Forced vital capacity and 6‑minute walk distance also improved during early follow‑up, while transfer factor of the lung for carbon monoxide 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 who underwent paired magnetic resonance imaging. Higher baseline level of vascular endothelial growth factor D (VEGF‑D) was associated with lymphatic involvement, and decreased during treatment. Adverse events were mostly mild; permanent discontinuation occurred in approximately 6% of the patients.

CONCLUSIONS

In routine practice, sirolimus treatment was associated with long‑term stabilization of lung function, marked improvement of lymphatic disease, reduction of angiomyolipoma burden, and acceptable tolerability. VEGF‑D level aligned with lymphatic phenotype and declined with treatment, thus supporting its role as a monitoring biomarker.