What is Lymphangioleiomyomatosis (LAM)?

From the Guidelines

Lymphangioleiomyomatosis (LAM) patients with abnormal or declining lung function should be treated with sirolimus rather than observation. This recommendation is based on moderate-quality evidence from the official American Thoracic Society/Japanese Respiratory Society clinical practice guidelines 1. The goals of sirolimus therapy are to stabilize lung function, improve functional performance, and improve overall quality of life 1.

Key Considerations

• Sirolimus is the only FDA-approved medication for LAM and has been shown to stabilize lung function.
• The standard dose of sirolimus is 1-2 mg daily, adjusted to maintain blood levels between 5-15 ng/mL, with regular monitoring required.
• Supportive care includes bronchodilators for airflow obstruction, oxygen therapy when needed, and management of complications like pneumothorax or chylous effusions.
• Hormonal therapies, including progestins, gonadotrophin-releasing hormone agonists, selective estrogen receptor modulators like tamoxifen, and oophorectomy, are no longer recommended as first-line treatment due to limited evidence 1.
• Lung transplantation may be considered for advanced disease.

Management and Monitoring

• Patients should be followed by specialists familiar with LAM and undergo regular pulmonary function tests.
• Estrogen-containing medications should be avoided as they may worsen the disease.
• Sirolimus inhibits the mTOR pathway, which is activated due to mutations in the TSC1 or TSC2 genes, leading to the abnormal growth of smooth muscle-like cells in LAM patients 1.

Treatment Approach

• Sirolimus is the preferred treatment for LAM patients with abnormal or declining lung function, with a strong recommendation based on moderate-quality evidence 1.
• The treatment approach should be individualized, taking into account the patient's values and preferences, as well as the clinical situation at hand.

From the Research

Overview of Lymphangioleiomyomatosis

• Lymphangioleiomyomatosis (LAM) is a rare disease considered a low-grade neoplasm with metastatic potential and variable progression 2.
• It is characterized by cystic lung disease resulting in progressive dyspnea, renal angiomyolipomas, and lymphatic complications 3.

Treatment Options

• Mechanistic target of rapamycin (mTOR) inhibitors, such as sirolimus and everolimus, have become a treatment option for LAM patients, especially those with extrapulmonary manifestations 2, 4, 5.
• Sirolimus has been shown to improve pulmonary function and decrease chylous effusion in patients with LAM, even at low doses (trough level, 5ng/mL or less) 6.
• Everolimus has also been shown to improve some measures of lung function and exercise capacity, and reduce serum vascular endothelial growth factor-D (VEGF-D) and collagen IV levels 5.

Management and Prognosis

• Pneumothorax occurs frequently (70%) in LAM patients, and definitive management with pleurodesis is recommended due to the high risk of recurrence 3.
• Life expectancy in patients with LAM is favorable, with a mean transplant-free survival of over 20 years from the time of diagnosis 3.
• Administration of an mTOR inhibitor until lung transplantation may decrease waitlist mortality, and a reduced dose until transplantation is permissible 4.

Diagnostic Approach

• Characteristic thin-walled cysts are seen on computed tomography, and the presence of elevated serum levels of VEGF-D has good diagnostic specificity 3.
• No single clinical or serological factor has been shown to predict prognosis, but continued advances in understanding the molecular basis of LAM may lead to improved therapeutic targets and prognostic indicators 3.