Cancer; Heart

AL amyloidosis treatments offer patients hope and potentially a cure

Cancer; Heart

In AL amyloidosis, the “A” stands for amyloid, and the “L” stands for light chain. Light chains are components of antibodies made by plasma cells in the bone marrow. In AL amyloidosis, a group of plasma cells makes too many light chains, which misfold and clump together to form amyloid fibrils. The fibrils are then deposited in the nerves and organs, coating them like wet cement. In this image, the pink background shows cells that are negative for amyloid. The second image shows AL amyloidosis under the microscope. The misfolded protein refracts and appears a characteristic apple-green color.

AL amyloidosis is oftentimes a confusing and overwhelming diagnosis for a patient.

This bone marrow disorder, which is characterized by “misfolded” proteins, defies traditional disease classification. It can affect an array of cells, nerves, and organs, so it can’t be treated solely as a cancer, bone disease, or cardiovascular condition.

AL amyloidosis also causes a wide spectrum of symptoms because the abnormal proteins that break down into a substance called amyloid coat a patient’s nerves and organs like wet cement, creating the potential for:

  • Diffuse pain
  • Diarrhea or constipation
  • Dizziness, fatigue, and shortness of breath
  • Frequent nighttime urination
  • Heart, kidney, and liver problems
  • Irregular heartbeat
  • Neuropathy (nerve pain or numbness)
  • Excess protein in the urine
  • Skin changes (easy bruising, purple discoloration around the eyes)
  • Swelling in the ankles and legs
  • Unintended weight loss

Each year, 4,500 new cases of AL amyloidosis are diagnosed in the U.S., approximately two-thirds of which are in men ages 50-80. There is no way yet to predict which nerves or organs a given patient’s disease will affect and to what extent. AL amyloidosis has no set preference for one organ over another.

Without appropriate and prompt treatment, the median survival with AL amyloidosis is five to seven months. In January 2021, however, the U.S. Food and Drug Administration (FDA) approved the first four-drug combination to treat newly diagnosed light-chain AL amyloidosis, and it is showing impressive results right out of the gate. Patients may experience a nearly 30% boost in healthy blood cell response and improved organ function and longevity.

At UT Southwestern, our amyloidosis team is at the forefront of researching and treating this complex disease, and we work closely with an array of specialists to develop a customized treatment plan for each patient. In some cases, we are even able to offer a potentially curative combination of immunotherapy, chemotherapy, and a bone marrow/stem cell transplant using the patient’s own healthy cells derived from the bone marrow (stem cells).

AL amyloidosis is an aggressive condition with individual symptoms that vary from patient to patient. Diagnosing and treating it effectively requires the collaboration of a multidisciplinary team of experts like ours that is focused on finding the latest medical therapies to give patients a chance at longer, healthier lives.

Diagnosing AL amyloidosis

As with any life-threatening condition, early detection is key. For AL amyloidosis, blood and urine tests can detect the presence of amyloid proteins (antibodies) six to nine months before symptoms become severe enough that patients wind up in the hospital or emergency room. MRI scans can also help to detect organ damage. However, bone marrow testing and biopsy are the only definitive methods to diagnose AL amyloidosis.

First, we take a biopsy of the patient’s bone marrow or from their affected organ (skin, cardiac muscle, etc.). We apply a special staining dye to the sample and use a spectrometer – a device that measures reactions between light and matter – to determine whether the patient has AL amyloidosis, ATTR amyloidosis, or any of the other 30 subtypes of amyloidosis.

Approximately 95 percent of amyloidosis cases that affect the heart are classified as either AL or ATTR cardiac amyloidosis:

  • AL is the most common type and is caused by a bone marrow disorder, but it can affect multiple organs.
  • ATTR can be either hereditary (caused by a mutation in the TTR gene) or wild-type (not associated with a genetic mutation). Both ATTR and AL amyloidosis can cause cardiac amyloidosis, a condition in which amyloid deposits cause heart muscle tissue to stiffen, preventing the heart from contracting and relaxing normally during heartbeats.

Not uncommonly, AL amyloidosis is misdiagnosed as multiple myeloma, a cancer that also forms in the bone marrow. Patients can have both conditions simultaneously. The conditions have some similarities, but are, in the end, distinct:

  • AL amyloidosis attacks a patient’s heart, kidneys, liver, and other vital organs.
  • Multiple myeloma targets the bones.
  • Multiple myeloma is more common than AL amyloidosis.
  • There are many more FDA-approved medications for multiple myeloma.

Related reading: New drugs for cardiac amyloidosis provide hope for patients

Early detection and a team approach

AL amyloidosis is aggressive and uncommon, which means some patients get referred to many specialists before being accurately diagnosed. All the while, their condition is worsening.

For the best chance at positive outcomes, patients with protein in their urine and vague, systemic symptoms should be evaluated by an amyloidosis expert who is part of a multidisciplinary team.

Dr. Justin Grodin

Justin Grodin, M.D., M.P.H., a cardiologist, helps lead UT Southwestern’s Multidisciplinary Amyloidosis Program. We evaluate and care for patients from around the Southwest, working closely with our cardiologist, nephrologist, geriatrics, gastroenterology, neurology, psychology, and physiatry colleagues. Together, we narrow down each patient’s diagnosis and develop a personalized treatment plan to improve their organ function, control symptoms, and slow disease progression.

We often tell patients that treating amyloidosis is like encountering a flooding kitchen sink. First, we must stop the problem at its source – turn off the faucet before we start mopping the floor. Immunotherapy affords us the tools to potentially stop the flow of misfolded proteins in the bone marrow. Novel therapies are under clinical investigation that focus on eliminating amyloid protein from the organs, i.e., mopping the floor.

Systemic therapy and stem cell transplant

Our AL amyloidosis patients typically undergo treatment for six months to two years. In some cases, treatment can be curative.

The first goal for treating newly diagnosed patients is to improve organ function. Along with a three- or four-drug combination of AL amyloidosis medication, treatment may also include medications to support the patient’s affected nerves or organs.

If the patient’s organ function improves, they may grow strong enough to withstand a combination of immunotherapy, chemotherapy, and an autologous bone marrow/stem cell transplant that uses the patient’s own healthy bone marrow cells (stem cells).

Ideally, the process goes as follows:

  • Immunotherapy wipes out damaged cells from the bone marrow.
  • We harvest healthy stem cells, which we freeze for transplantation.
  • Chemotherapy eliminates microscopic remnants of damaged cells that are potentially circulating in the bone marrow.
  • Then, we transplant the healthy cells back into the patient’s bone marrow.

In successful cases, the transplanted stem cells grow and generate new, healthy cells, essentially curing the condition.

Getting care from a multidisciplinary center – where experts in all phases of treatment are available 24/7 – greatly increases a patient’s chances for positive outcomes.

The future of AL amyloidosis care

UT Southwestern contributes to the Cardiac Amyloidosis Registry Study, a national database of anonymized patient data, and Dr. Grodin is on the steering committee. By analyzing the registry, we can see trends in outcomes for patients with various forms of amyloidosis who try certain treatments.

Here at UT Southwestern, we are participating in several translational studies in which we are analyzing existing research to find potential clinical applications for treatment approaches or medications. Explore amyloidosis clinical trials at UT Southwestern.

We are also preparing to research another novel compound Belantamab Mafodotin (Blenrep), which was recently approved for multiple myeloma. It is a stand-alone medication rather than a combination of drugs. We are currently awaiting approval from the FDA to conduct an investigational drug study. The drug is manufactured by GlaxoSmithKline, which provided support to UTSW to run a multi-institutional clinical trial for this novel medication.

Treatment advances, such as the new four-drug combo, that add the new injectable drug daratumumab plus hyaluronidase (Darzalex Faspro) to the standard three-drug combo of bortezomib, cyclophosphamide, and dexamethasone, are very encouraging for patients and providers.

Combined with early diagnosis and multidisciplinary care, patients with AL amyloidosis can have the opportunity for longer lives with fewer symptoms – and potentially a cure for their disease.

To visit with an amyloidosis expert, call 214-645-8300 or request an appointment online.

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Expert amyloidosis care

UT Southwestern is the only academic medical center in Texas with a Multidisciplinary Amyloidosis Program, which gives patients access to the most advanced care, research, and clinical trials in the region.

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