When Sally Cox was diagnosed with light chain amyloidosis (AL) in 2019, she was shocked. Not only had she never heard of the rare disease that causes abnormal proteins (or amyloids) to build up in your tissues and organs, the more she learned, the more she realized how devastating it was.
“I was diagnosed on a Friday at 5 p.m. and told ‘You’ve got six months to live,’” said the Seattle 60-year-old who owns an organic food business. “Then the doctor said to make an appointment to see her in three to four weeks! Instead, I went online and found an amyloidosis support group. They put me in touch with Fred Hutch and UW Medicine.”
Cox said the most disturbing thing she discovered about the disease was that there were no FDA-approved treatments for it, the main reason she agreed to participate in a clinical trial.
Amyloidosis is not a cancer, but it is associated with the blood cancer multiple myeloma and in the past, patients were treated with similar protocols. Clinical trials, the means by which new therapies are tested out on patients in order to gain approval from the U.S. Food & Drug Administration, have been crucial in finding effective treatments for the condition.
But before a person can enroll in a clinical trial, they must first be diagnosed. And that’s often a problem for these patients.
“It only took me two hematologists to diagnosis it,” Cox said. “I was fortunate to be diagnosed so quickly. Sometimes people can go several years and go to many different doctors only to find out too late the amyloidosis has damaged vital organs such as the heart and kidneys.”
— Fred Hutch hematologist-oncologist and clinical researcher Dr. Andrew Cowan
Fred Hutch Cancer Center’s Andrew Cowan, MD, who treats the disease, said delayed diagnosis is unfortunately quite common.
“It’s an uncommon condition, so physicians often don’t consider the diagnosis,” he said. “It’s often diagnosed at a more advanced stage. Although survival has improved, some patients, especially those with advanced cardiac involvement, still don’t benefit as much from therapy.”
In light chain amyloidosis, abnormal plasma cells, which normally make protective immune proteins called antibodies, instead produce amyloidogenic light chains (a component of antibodies). These light chains misfold, depositing in various tissues and organs throughout the body.
Depending on where they land, the symptoms can be subtle or sudden, as in the pulmonary edema that Cox experienced while snorkeling in Hawaii.
That was her first indication that anything was wrong.
“I almost drowned due to massive pulmonary edema, but I was very physically fit and didn’t have the typical indications for someone with cardiomyopathy, which would have caused that,” she said. “Also, I didn’t have diabetes. So they went down the rabbit hole of rare diseases.”
Cowan said the deposits can cause issues with multiple organs over the years, although some people have few symptoms until the condition is prevalent.
“When they’re in the tissues, the amyloid fibrils are like concrete, they’re stiff,” he said. “Over time, the deposits affect the organs and then they can’t function properly. And it can happen to almost any organ.”
There are also different forms of the disease, including one that’s hereditary (transthyretin or TTR amyloidosis). Most people, like Cox, are diagnosed with AL amyloidosis, also known as primary amyloidosis. There are no known ways to prevent it.
The main reason for late diagnoses is that warning signs and symptoms can be nebulous and are often mistaken for other conditions.
People with amyloidosis deposits in their heart, for instance, may have shortness of breath, abnormal heart rhythm, chest pain, fainting or difficulty with physical activity.
“With cardiac amyloidosis, your heart hardens and loses its ability to pump blood efficiently,” Cox said. “It doesn’t feed blood to the left ventricle adequately. It’s cardiomyopathy to the extreme. When I was diagnosed, the doctor said my heart would never get better. They’re not saying that now, though. A recent CT scan showed my heart is healing.”
Kidney-related symptoms include decreased urine output, foamy urine and swelling in the lower legs, belly, arms and lungs. Nerve-related symptoms of amyloidosis include pain, numbness or tingling (also known as peripheral neuropathy) in the hands or feet; dizziness when standing quickly; bowel problems or erectile dysfunction and carpal tunnel syndrome. An enlarged tongue — known as macroglossia — can also be a symptom. Read more about the signs and symptoms of this condition here.
“Over time, folks with renal amyloidosis can develop end-stage renal disease and require dialysis,” Cowan said. “If it lands in the heart, patients can develop heart failure. We can consider heart transplants for a few patients, but in general if the damage is done, it can often be challenging to reverse. I’ve lost too many patients in the first six to 12 months after diagnosis because it took them forever to get a diagnosis.”
As with cancer, the earlier the diagnosis, the likelier the patient can be treated successfully.
“There were few treatments really when I was diagnosed,” Cox said. “But that was back in the day, five years ago.”
Her participation in a clinical trial changed that.
“It was a small clinical trial but my doctor said they couldn’t even find 300 people around the world to participate,” she said. “So I signed on. There really was no other option. It was the only shot to get the experimental trial drug approved.”
Cox hoped to receive the trial drug, but instead she was randomized to the standard of care arm. Fortunately, her amyloidosis responded.
“I got a very good partial response, although I did not get a complete response,” she said. “The new drug had a complete response rates of like 85%, which was a huge breakthrough. But now I have that drug in my back pocket, which I can try in case I relapse.”
Cox also has something else: the knowledge that her participation in the clinical trial actually ended up helping a member of her own family, her 76-year-old sister-in-law, Ethel Horn.
Horn had been having health issues for nearly two years, most recently a bout of carpal tunnel in her left hand.
“I had all kinds of tests and nobody could find anything wrong,” she said. “Then I got carpal tunnel which got worse and worse and started going up my arm.”
Horn went to her primary care physician, who suggested surgical release, a common procedure for carpal tunnel. She also had a chat with her orthopedic surgeon about a “jellyfish-like bubble” under the skin of her left wrist. The surgeon thought it might be a cyst and said he’d remove it during the procedure.
Luckily, a pathologist tested the mass for amyloidosis using an assay known as Congo red dye. Horn was informed of the test and its positive results but didn’t know the significance until she mentioned it during dinner a few days later at Cox’s house. Her reaction was immediate.
“Sally just gasped and said ‘Oh my God! You need to get in to see somebody right now!’” Horn said. “The Congo red tipped her off. The thing on my wrist was evidently full of misfolded proteins. She got me in to see her doctor that Monday and they were really surprised to catch it this early. It was another two to three weeks before my orthopedic team reached out and told me I had light chain amyloidosis. I said, ‘I know.’”
Cowan, a clinical researcher as well as a hematologist-oncologist, is treating both patients. He said it was highly unlikely for two women from the same family to be diagnosed with the same disease.
“Amyloidosis is incredibly rare,” he said. “The diagnosis rate of light chain amyloidosis is 10 per million. What are the odds?”
Also highly unusual, the trial that Sally participated in, known as Andromeda, actually ended up helping her own husband's sister.
“That was a practice-changing trial,” Cowan said. “Daratumumab is the standard of care now and that’s what Ethel is on. Sally contributed and Ethel ended up benefitting. It’s participation in trials that changes outcomes for patients. Sally wasn’t on the experimental arm; she was on the control arm, but she still played a role in Ethel getting the newly approved drug.”
Cox said she’s doing great these days. She’s able to work, her heart is improving and she’s enthusiastic about her clinical trial participation and other advocacy efforts.
“I was really happy somebody I knew actually benefited,” she said. “I would love to help get more people enrolled in these trials so there are more therapies.”
These days, she’s trying to raise awareness among surgeons performing carpal tunnel release surgeries, encouraging them to order the Congo red dye test to check for amyloidosis in these patients.
“In the early stages of amyloidosis, carpal tunnel — especially bilateral carpal tunnel — may be one of the first symptoms to show,” she said. “If we can catch it early before it attacks vital organs, it’s a much more manageable disease. And now there are a lot more promising therapies.”
Cowan said he’s grateful to have such a “fireball” as a patient.
“Sally has tons of energy and is very motivated and I think that’s great,” he said. “We need to work across disciplines to help improve awareness and carpel tunnel is a great example of where we can do better.”
He also said he’s eager to work with Fred Hutch and UW Medicine colleagues to find an automated way for carpal tunnel patients to get biopsies with the Congo red stain.
“It’s not early detection, but it’s making sure nothing falls between the cracks,” he said.
Cowan is also looking forward to results from current clinical trials as well as those looking at early detection. In the meantime, he continues to see patients and to appreciate the many contributions they make to science.
“Patients put their blood, sweat and tears into these clinical trials and it’s completely altruistic,” he said. “It’s like having a second job. They’re here all the time; they have to go through tons of tests. And they may or may not get something out of it. There’s no guarantee of anything other than contributing to making the science better.”
Diane Mapes is a staff writer at Fred Hutchinson Cancer Center. She has written extensively about health issues for NBC News, TODAY, CNN, MSN, Seattle Magazine and other publications. A breast cancer survivor, she blogs at doublewhammied.com and tweets @double_whammied. Email her at dmapes@fredhutch.org. Just diagnosed and need information and resources? Visit our Patient Care page.
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