Long-term sirolimus treatment in lymphangioleiomyomatosis

Introduction: Lymphangioleiomyomatosis (LAM) is a rare slowly progressive neoplasic disease that leads to respiratory failure. Short-term treatment with siroliumus has shown to stabilize pulmonary function but data on long-term results lack. The aim of this study was to describe the long-term impact of sirolimus treatment. Methods: From November 2007 to October 2018, 46 LAM patients treated with sirolimus from a tertiary referral centre were retrospectively included. Sirolimus response at 1 year was evaluated. A negative response was defined as a decrease in FEV1 greater than 20 mL/year considered to be the physiological age-related decline. The response was revaluated after 5 years of treatment. Results: 11 (24%) from 46 patients were treated with sirolimus for less than 1 year, 35 (76%) for more than 1 year and 24 (52%) for at least 5 years. A positive response to sirolimus at first year was observed in 21 (60%) patients. Mean pulmonary function test values after one year of sirolimus treatment were FVC 3377 (SD 864) mL, FEV1 2221 (SD 862) mL, and DLCO 56% (SD 21), in the responder group and FVC 2763 (SD 960) mL, FEV1 1736 (743) mL and DLCO 47% (SD 16) in the non-responder group (p<0.05 for FEV1 and FVC). After 5 years of treatment, 66% of the patients maintained the positive response. All patients except one with initial negative response kept the same response at 5 years. Conclusion: Our study supports the idea that sirolimus treatment has a positive long-term impact in nearly half of LAM patients. This is the first study that provides pulmonary function values at 1 and 5 years in LAM patients treated with sirolimus.