Systemic amyloidoses are rare. In this group of related diseases, an abnormally folded protein forms a substance called amyloid. It can build up in one or more organs, such as the kidney, heart, or liver. It can also accumulate in nervous system tissue. The most common type of amyloid is made of immunoglobulins produced by plasma cells in the bone marrow.

As amyloid builds up, it can prevent the organs from working properly and eventually cause them to fail.

There are four major forms of systemic amyloidoses:

• AL amyloidosis (or primary systemic amyloidosis)
• familial amyloidosis
• senile systemic amyloidosis
• secondary amyloidosis

Treatment for systemic amyloidoses is usually aimed at limiting amyloid production.

Symptoms of Systemic Amyloidoses

Symptoms of systemic amyloidoses can include:

• weakness or fatigue
• weight loss
• heart damage (congestive heart failure) or irregular heart rhythm
• shortness of breath
• swelling of the feet or legs due to accumulation of fluid
• stomach discomfort on the right side
• abdominal swelling
• early fullness with eating
• gastrointestinal bleeding
• chest pains
• lightheadedness (due to the lowering of blood pressure during sudden position changes)
• numbness or tingling in the lower extremities (called peripheral neuropathy)

AL Amyloidosis (Primary Systemic Amyloidosis)

The most common form of systemic amyloidosis is systemic light chain amyloidosis. It is also called AL amyloidosis or primary systemic amyloidosis. AL amyloidosis is diagnosed in approximately 3,000 people in the United States each year. However, many experts think it is actually underdiagnosed. They suggest that primary care doctors may not recognize when and how to test for AL amyloidosis.

In people with AL amyloidosis, abnormal plasma cells produce an immunoglobulin light-chain protein that forms the amyloid. Over time, these light-chain proteins build up in different organs. This amyloid prevents the organs from working normally and potentially causes serious damage.

AL amyloidosis is rare, but our doctors care for numerous people with the disease. This extensive experience enables them to make an accurate diagnosis and to select the best course of treatment based each patient’s needs.

To diagnose AL amyloidosis, our doctors use a number of tests. Blood and urine tests look for the presence of the abnormal immunoglobulin light-chain proteins. Imaging tests detect damage to the heart or other organs that may be affected. Other tests include a bone marrow biopsy or a biopsy from an affected organ or part of the body with many blood vessels, such as abdominal fat or the rectum.

Treatment for AL Amyloidosis

Therapies for AL amyloidosis are aimed at eliminating the abnormal plasma cells and removing the immunoglobulin light-chain proteins that cause amyloid. Our doctors plan treatment for people with AL amyloidosis based on a variety of factors, including the risk of side effects.

There are no drugs approved specifically for the treatment of AL amyloidosis. Treatment used for multiple myeloma can be effective for AL amyloidosis too. Because their organs aren’t always working as they should, people with AL amyloidosis often cannot take the same dose of these drugs as people with multiple myeloma.

To treat AL amyloidosis, our doctors usually combine traditional chemotherapy drugs such as melphalan (Alkeran^®) or dexamethasone (Decadron^®, Dexasone^®, Diodex^®, Hexadrol^®, Maxidex^®) with proteasome inhibitors such as bortezomib (Velcade^®).

Proteasome inhibitors block the activity of the proteasome. The proteasome is responsible for the removal of defective proteins. Because AL amyloidosis is a disorder of abnormal proteins, plasma cells in AL amyloidosis are often very sensitive to proteasome inhibitors.

Doctors at Memorial Sloan Kettering may recommend an autologous stem cell transplant for the treatment of AL amyloidosis. In an autologous stem cell transplant, the patient’s own blood-forming stem cells are isolated and frozen. After high-dose chemotherapy, the stem cells are returned via the bloodstream. A stem cell transplant is also called a bone marrow transplant.

To kill the plasma cells, very high doses of chemotherapy are given before a stem cell transplant. Patients are thoroughly tested before the chemotherapy to ensure that the heart, liver, and lungs are healthy enough to withstand the transplant.

If someone is not healthy enough for a stem cell transplant, he or she will likely receive chemotherapy as a primary treatment.

If AL amyloidosis has caused organ failure, an organ transplant may sometimes be considered. In this case, our doctors will refer an appropriate transplant center for specialized care.

New Approaches for Treating AL Amyloidosis

Recently our doctors began achieving excellent results by giving a second chemotherapy dose after a stem cell transplant in people whose AL amyloidosis persists. For people who are good candidates for stem cell transplantation, this has proven to be a safe and effective treatment.

With this approach, people first receive a high dose of the chemotherapy drug melphalan. They then undergo an autologous stem cell transplant. Following the transplant, a combination of the proteasome inhibitor bortezomib and dexamethasone (a cortisone/corticosteroid) is often used. Our experts have safely achieved a response rate in nearly 80 percent of people on this treatment. This includes a total removal of the abnormal plasma cells and immunoglobulin light-chain proteins in nearly 60 percent of people. A total removal is also called a complete response, and it is one of the highest rates ever reported in the treatment of AL amyloidosis.

Our doctors are also conducting clinical trials to investigate new treatment approaches for AL amyloidosis. These trials include antibodies (called NEOD001) toward AL amyloid deposits, the proteasome inhibitors ixazomib (Ninlaro^®) and carfilzomib (Kyprolis^®), antibodies toward plasma cells (daratumumab, called by the brand name Darzalex^®), and chemotherapy (bendamustine, called by the brands Treanda^® and Bendeka^®).

Other Forms of Amyloidosis

There are three other major forms of amyloidosis: familial amyloidosis, senile systemic amyloidosis, and secondary amyloidosis. They are even more rare than AL amyloidosis. Our doctors are experienced at diagnosing these disorders, but they do not routinely treat them. Instead, they refer people with these amyloidosis types to appropriate specialists for supportive management, organ transplantation, or treatment of the condition causing the disease.