What is the treatment for Lymphangioleiomyomatosis (LAM)?

From the Guidelines

Lymphangioleiomyomatosis (LAM) treatment should focus on managing symptoms and slowing disease progression, with sirolimus (rapamycin) being the primary medication, as recommended by the American Thoracic Society and Japanese Respiratory Society clinical practice guidelines 1. The primary goal of treatment is to stabilize lung function, improve functional performance, and improve overall quality of life. Sirolimus works by inhibiting the mTOR pathway, which is overactive in LAM cells, helping to reduce complications. Some key points to consider in LAM treatment include:

• Sirolimus is typically started at 1-2 mg daily and adjusted to maintain blood levels between 5-15 ng/mL, as supported by the guidelines 1.
• Bronchodilators like albuterol may be prescribed for breathing difficulties.
• Oxygen therapy is recommended when blood oxygen levels fall below 88-90%.
• For patients with recurrent pneumothorax (lung collapse), pleurodesis might be necessary to prevent recurrence.
• Hormone therapy with progesterone was historically used but has limited evidence supporting its effectiveness, and is not recommended by the guidelines 1.
• Lung transplantation remains the ultimate treatment option for advanced cases with severe respiratory impairment, with both single and bilateral lung transplantations being viable options 1. Regular pulmonary function tests every 3-6 months are essential to monitor disease progression. Patients should avoid smoking and estrogen-containing medications, as these can worsen the condition. A pulmonologist with experience in interstitial lung disease should oversee treatment, as LAM management requires specialized expertise.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Treatment Options for LAM

• The treatment for Lymphangioleiomyomatosis (LAM) has been mostly symptomatic and supplementary until the advent of mammalian target of rapamycin (mTOR) inhibitors 2, 3, 4, 5, 6.
• mTOR inhibitors, such as sirolimus and everolimus, have shown significant improvement in patients with LAM, especially those with extrapulmonary manifestations 2, 3, 4, 5, 6.
• The use of mTOR inhibitors has been shown to stabilize lung function in patients with LAM 2, 3, 4, 5.
• Sirolimus has been used to treat patients with LAM, resulting in resolution of severe chylothorax, reduction in renal angiomyolipoma volume, and regression of retroperitoneal lymphangioleiomyomas and abdominal lymph node enlargement 4, 5.

Administration and Efficacy

• The optimal dose and duration of treatment with mTOR inhibitors have yet to be sufficiently clarified 3, 4.
• The treatment with mTOR inhibitors has been shown to be effective in patients with different extrapulmonary manifestations, such as renal angiomyolipoma, lymphangioleiomyomas, and chylous effusions 4.
• The side effects of mTOR inhibitors have been well managed in patients with LAM 2.

Future Directions

• Further investigation is needed to refine the currently available therapeutic applications and to develop novel remedies for LAM 3.
• Other treatment options, such as targeting LAM cell survival and metastasis, are being investigated and tested in clinical trials 6.
• The destruction of lungs, pathological lymphangiogenesis, and hormonal regulation are key remaining and poorly understood areas for development and validation of therapeutic targeting in LAM 6.