There are several options in managing LAM. Patients and physicians should make therapy decisions jointly after thorough discussion of the risks and benefits of all options.
mTOR Inhibitor Therapy
Long-term treatment with an mTOR inhibitor is generally recommended for patients who have abnormal lung function and evidence of progressive lung function decline. mTOR therapy is also effective in patients with refractory chylous effusions. Trials are planned to determine if early low dose sirolimus therapy can prevent progression to more advanced stages
- RAPAMUNE® (sirolimus) is the first drug to be approved by the FDA for the treatment of LAM. It is a highly specific inhibitor of the mechanistic target of the rapamycin (mTOR) signaling pathway that is dysregulated in LAM cells. Treatment with the drug suppresses growth of LAM cells and likely shrinks them, without killing them. It also reduces bad behaviors of LAM cells, such as production of VEGF-D that likely enhances tissue damage and the spread of LAM through the body. Sirolimus has been shown to stabilize lung function and improve quality of life in patients with moderate to severe LAM.
- Afinitor (everolimus) is also used in the treatment of LAM, although it is not FDA approved for that purpose. Everolimus has been shown to be effective for the treatment of angiomyolipomas and subependymal giant cell astrocytomas in patients with tuberous sclerosis. It is a derivative of sirolimus and has very similar functions and side effects.
- Oxygen therapy may become necessary as LAM progresses and lung function becomes impaired. In addition, oxygen may prolong life in hypoxic patients. Oxygen should be administered to maintain arterial oxygen saturations of 90% or greater. It will also support rest, exercise and sleep and may help stabilize pulmonary hypertension.
- Bronchodilators may benefit patients. About 25% of LAM patients have an asthma-like component that responds to bronchodilators. Many LAM patients benefit from the use of drugs such as albuterol, formoterol and salmeterol.
- Anti-estrogen therapies. Although patients with LAM have been managed empirically with anti-estrogen therapies for decades, there is no proof that they are effective. In addition, induction of early menopause is distressing and morbid in young women. Clinicians sometimes consider hormonal therapies in special situations, such as progression of lung function decline despite sirolimus use and in patients who have recurrent pneumothoraces that are timed with the menstrual cycle.
- Progestins can cause fluid retention and mood swings. They are no longer routinely used in patients with LAM.
- Gonadotrophin-releasing hormone (GnRH) antagonists (receptor blockers), such as LUPRON® (leuprolide), induce menopause. Their role in the treatment of LAM is unclear. The risk of bone and cardiac disease is increased.
- Corticosteroids, immunomodulatory cytotoxic agents or ovarian irradiation are not recommended.
- Oophorectomy (removal of the ovaries) is no longer routinely recommended in LAM patients. The procedure is invasive without clear evidence of efficacy. In addition, the risk of bone and heart disease is increased.
Referral for evaluation for lung transplantation should be considered when the FEV1 approaches 30%. Patients may also be eligible based on other factors that profoundly affect quality of life, such as disabling shortness of breath or problems maintaining oxygen saturation despite high supplemental oxygen delivery rates. Both single and bilateral lung transplantation have been performed for patients with LAM and both are suitable options. One, five, and ten-year survival rates after lung transplantation are 89%, 67%, and 47%, respectively.