Amyloid light-chain (AL) amyloidosis is a rare condition that happens when abnormal proteins called light chains build up in the body’s tissues and organs. There are several types of amyloidosis, and AL amyloidosis is the most common form. It can affect nearly any part of the body but commonly involves the heart, kidneys, liver, and peripheral nerves (nerves outside the brain and spinal cord).

In the United States, diagnoses of AL amyloidosis appear to be increasing. Early awareness is key to helping people receive faster, more accurate diagnoses and start treatment before the disease causes serious organ damage. Getting treatment sooner can improve both quality of life and survival.

Read on to learn more about AL amyloidosis — also called primary amyloidosis — including its causes, common symptoms, and treatments.

What Causes AL Amyloidosis?

To understand AL amyloidosis, it helps to know how this disease develops. Antibodies (also called immunoglobulins) are proteins made by the immune system to help fight infections. They’re produced by plasma cells, a type of white blood cell. Each antibody is made of two types of protein parts: heavy chains and light chains.

In AL amyloidosis, the body makes abnormal light chains that are misshapen (misfolded). These misfolded light chains clump together to form amyloid fibrils — sticky protein deposits that build up in tissues and organs. Over time, these deposits can interfere with how organs function and may cause serious damage.

Is Light-Chain Amyloidosis a Cancer?

AL amyloidosis is not a type of cancer, but it can be linked to certain cancers in some people. Around 10 percent to 15 percent of people with AL amyloidosis also have multiple myeloma — a blood cancer that affects plasma cells.

Having both AL amyloidosis and multiple myeloma can make treatment more complex. That’s why it’s important to test for both conditions early and build a care plan that addresses each.

Even in people who don’t have cancer, AL amyloidosis is a serious condition. Toxic amyloid deposits — and the fibrils that make them up — can build up in vital organs and cause damage. When these protein buildups affect the heart, it’s called cardiac amyloidosis.

Who Gets AL Amyloidosis?

When learning how common a disease is, researchers often use two key terms: “prevalence” and “incidence.”

• Prevalence is the total number of people living with a disease at a specific time.
• Incidence refers to the number of new cases diagnosed within a certain period.

A 2023 U.S. study found the yearly incidence rate of AL amyloidosis to be 16.7 new cases per million people. The prevalence was reported at 69.1 cases per million people. These numbers can vary depending on the population studied and the tools used for diagnosis.

Because AL amyloidosis is rare, many hospitals and medical centers may not be equipped to recognize or manage it properly. This can lead to delays in diagnosis and treatment, which underscores the need for greater awareness among both doctors and the public.

What Are Risk Factors for Developing AL Amyloidosis?

Several factors can increase a person’s risk of developing AL amyloidosis. These include age, biological sex, and certain health conditions, such as myeloma or diabetes.

Age

The risk of developing AL amyloidosis increases with age. Most people are over age 40, and the chance of developing the condition goes up as people get older. This is partly because plasma cell disorders — which cause AL amyloidosis — are more common in older adults.

Biological Sex

AL amyloidosis is more common among males than females, according to research in Methodist DeBakey Cardiovascular Journal. Specifically, the ratio of affected males to females is about 3 to 2. Researchers are still studying why this difference exists.

Other Health Conditions

AL amyloidosis is sometimes linked to other diseases. Research shows that people with this condition are more likely to also have:

• Multiple myeloma (a cancer of plasma cells)
• Diabetes
• Hypothyroidism (low thyroid hormone levels)

How Is AL Amyloidosis Diagnosed?

Diagnosing AL amyloidosis can be a lengthy and sometimes complex process. The first steps usually include blood and urine tests to look for monoclonal proteins — abnormal proteins made by plasma cells. These proteins are often a key sign of AL amyloidosis.

Once your care team has the test results, they’ll decide whether more testing is needed. If so, you may need one or more of the following:

• Tissue biopsy — A small sample of tissue is taken to check for amyloid deposits in affected organs.
• Bone marrow biopsy — This helps determine if your plasma cells are abnormal or overproducing light chains.
• Echocardiogram — This ultrasound of the heart checks how well it’s working.
• MRI or other imaging scans — These are used to examine the health of other organs, such as the liver or kidneys.

After testing, your healthcare provider will review the results with you, explain what they mean, and talk through next steps. This may include confirming a diagnosis, identifying organ involvement, and discussing a treatment plan.

What Are the Symptoms of AL Amyloidosis?

AL amyloidosis symptoms occur when amyloid proteins build up in the body’s organs and tissues. These deposits can affect the kidneys, heart, digestive system, and nervous system, and symptoms often appear in more than one area of the body.

The symptoms can be nonspecific (similar to other conditions), which is one reason a diagnosis may be delayed.

Common symptoms of AL amyloidosis include:

• Irregular heartbeat
• Shortness of breath
• Severe fatigue (exhaustion that does not improve with rest)
• Muscle weakness
• Swelling in the legs, feet, or abdomen (belly)
• Appetite changes
• Macroglossia (enlarged tongue)
• Peripheral neuropathy (numbness, tingling, or pain in the hands or feet)
• Digestive symptoms, such as diarrhea or constipation
• Frequent urination
• A purplish rash or bruising around your eyes
• Carpal tunnel syndrome

Everyone’s experience with AL amyloidosis is different. Some people may have only a few symptoms, while others may notice many. If you’re experiencing any of these signs — especially in combination — it’s important to talk to your doctor.

How Is AL Amyloidosis Treated?

Treatment for AL amyloidosis depends on several factors, including your age, overall health, and whether you have any other medical conditions. It’s important to work with a doctor who specializes in treating amyloidosis so you can explore the most current treatment options together.

Treatments for AL amyloidosis may include:

• Chemotherapy — This uses medication to stop abnormal plasma cells from making harmful light chains.
• Autologous stem cell transplant — Also known as a bone marrow transplant, this procedure involves high-dose chemotherapy (such as melphalan) followed by reintroduction of your own healthy stem cells.
• Other drug treatments — Options include medications that affect the immune system or target abnormal plasma cells.

Clinical trials are research studies that test new or emerging treatments for AL amyloidosis. Your care team can help you find trials you may be eligible for and talk with you about whether they might be a good fit.

FDA-Approved Treatments for AL Amyloidosis

The U.S. Food and Drug Administration (FDA) has approved two treatments for AL amyloidosis.

Daratumumab plus hyaluronidase (sold as Darzalex Faspro) was approved in 2021 to treat people who were recently diagnosed with AL amyloidosis. It’s used in combination with three other drugs — bortezomib, cyclophosphamide, and dexamethasone. This combination is designed to stop abnormal plasma cells from producing the light chains that form amyloid deposits. The medication is given as a quick subcutaneous (under the skin) injection into the abdomen. The process typically takes three to five minutes.

An earlier version of this drug, Darzalex, isn’t specifically approved for AL amyloidosis but may be prescribed off-label. This version is given through an intravenous (IV) infusion. The newer subcutaneous version is often faster and may be easier to tolerate for some people.

In 2023, the FDA also granted orphan drug designation to NXC-201, a form of chimeric antigen receptor (CAR) T-cell therapy. This treatment involves reprogramming your own immune cells (T cells) to recognize and fight the abnormal cells causing amyloidosis. Orphan drug status is given to treatments for rare diseases — defined as those affecting fewer than 200,000 people.

How Does AL Amyloidosis Progress, and What Is the Prognosis?

The progression and prognosis (outlook) for AL amyloidosis can vary greatly from person to person. It depends on which organs are affected, how early the disease is diagnosed, and how well it responds to treatment. Heart involvement is one of the most serious complications and is the leading cause of death related to AL amyloidosis.

One study looked at more than 2,000 people diagnosed with AL amyloidosis between 1980 and 2019. Among those diagnosed between 2010 and 2019, the median overall survival was 4.6 years. This means that more than half the people in that group lived longer than 4.6 years after diagnosis. That’s a significant improvement compared to those diagnosed in the 1980s, when the median survival was just 1.4 years.

It’s important to remember that each person’s experience with AL amyloidosis is different. Some people live much longer, especially with early diagnosis and newer treatments.

Talk to your doctor about your specific prognosis. They can explain how your individual health, organ involvement, and treatment plan affect your prognosis and help you make informed decisions moving forward.

Talk With Others Who Understand

MyAmyloidosisTeam is the social network for people with amyloidosis and their loved ones. On MyAmyloidosisTeam, more than 2,700 members come together to ask questions, give advice, and share their stories with others who understand life with amyloidosis.

Are you living with AL amyloidosis? What types of symptoms and treatments have you experienced? Share your experience in the comments below, or start a conversation by posting on your Activities page.