Safety and Durability of Sirolimus for Treatment of LAM

Lymphangioleiomyomatosis (LAM) is an uncommon disease affecting women. It is associated with
cystic lung destruction and progressive respiratory failure. The Multicenter International
LAM Efficacy of Sirolimus (MILES) Trial, led by the investigators' research team,
demonstrated that mTOR (mammalian target of rapamycin) inhibition with sirolimus was an
effective therapy that stabilized decline in FEV1 (forced expiratory volume). However, lung
function decline resumed when the drug was stopped at the one year point in MILES, suggesting
that therapy is suppressive rather than remission-inducing, and may need to be lifelong. The
investigators therefore need to know whether long-term therapy with sirolimus is safe and
effective. To accomplish this goal, the investigators will conduct the Multicenter
International Durability and Safety of Sirolimus in LAM Trial (MIDAS). This is an
observational "registry" trial. The investigators propose to enroll 300 LAM patients who are
on, have previously failed or been intolerant of or are considering taking sirolimus or
everolimus for clinical reasons in a longitudinal observational study. This registry will
follow lung function tests and adverse events over periods of at least 2 years. The mTOR
inhibitor therapy will be initiated and managed by the participant's clinician. The study is
planned to use the collected data from standard of care. This study will help us to refine
treatment for patients with LAM and determine if long term suppressive therapy with sirolimus
can prevent progression to later stages of disease. This research will be accomplished as
part of the Rare Lung Disease Clinical Network Consortium, with data stored and analyzed by
the Database Management Coordinating Center (DMCC) as part of the NIH-supported Rare Disease
Consortium.

Inclusion Criteria:

- Female, age 18 or over

- Diagnosis of LAM

- Signed and dated informed consent

- On chronic therapy, newly treated or may be considered for therapy with mTOR
inhibitors or previously intolerant of or having failed mTOR inhibitor therapy

Exclusion Criteria:

- Inability to attend at least one RLD Clinic visit per year

- Inability to give informed consent

- Inability or unwillingness to perform pulmonary function testing