The efficacy and safety of low-dose sirolimus for treatment of lymphangioleiomyomatosis

Everolimus for the treatment of lymphangioleiomyomatosis: a phase II study

“…A subsequent longer-term analysis of observational data from 38 patients with LAM with or without TSC reported that lung function stabilised during approximately 3.5 years of treatment with sirolimus, as demonstrated by slowing the decline of FEV1 and DLCO [41]. Additionally, a small retrospective study in 15 patients with LAM demonstrated that low-dose sirolimus improved lung function and chylous effusion [42], and an open-label trial in individuals with angiomyolipoma and LAM demonstrated significant improvements from baseline in FVC and FEV1 in women treated with sirolimus for 12 months, with no changes in 6-MWD or DLCO [26]. Positive though less impressive results were also reported for sirolimus in a second small series of patients, with shrinkage of angiomyolipomas observed but no clear improvement in lung function, although the number of patients available for analysis of pulmonary endpoints was small [27,43].…”

“…The dosing regimen in our study was determined prior to the MILES study and before additional data had been published. It has been suggested that lower doses of mTOR inhibitors may be effective in this patient population [25,42,46]. The optimal use and appropriate dosing of everolimus in the treatment of LAM requires additional investigation.…”

Treatment of lymphangioleiomyomatosis: building evidence in orphan diseases

“…mTOR inhibitors are responsible for many adverse events (including mouth ulcers, diarrhoea, nausea, increased blood cholesterol levels, skin rash and swelling of the extremities), most of which are manageable, yet preclude the long-term use of the drugs in a proportion of patients. A current approach is to use lower doses of mTOR inhibitors to improve their safety profile [25]; however, the benefit/risk ratio of lower doses has not been evaluated. Therefore, further investigation is needed to identify alternative pathways and pathogenic mechanisms involved in LAM and to develop novel therapies.…”

The changing face of a rare disease: lymphangioleiomyomatosis

“…A Japanese retrospective, observational study of 15 patients with LAM before and after therapy with serum levels of sirolimus <5 ng·mL −1 throughout the treatment period showed an improvement in the annual rate of change in FVC and FEV1 in the eight patients without chylous effusions. All but one of the remaining seven patients with chylous effusions experienced complete resolution of chylothorax and significant reduction of chylous ascites [131]. Except for a patient who developed a slight increase in parenchymal opacity on chest radiography and a patient who developed Aspergillus infection, the adverse events were mostly low grade.…”