Tracy George, MD, is the president of the Innovation Business Unit and chief scientific officer at ARUP Laboratories, a Utah-based nonprofit laboratory at the University of Utah’s Department of Pathology. She’s also a professor of pathology at the Spencer Fox Eccles School of Medicine at the University of Utah.
Systemic mastocytosis is a rare blood condition that affects roughly 13 in every 100,000 people. It happens when your body makes too many mast cells — a type of white blood cell that keeps your immune system working properly.
When mast cells detect something harmful, like a virus, they release a chemical called histamine. Histamine helps your immune system send messages between different cells, but most of us know it as the culprit behind an allergic reaction. In systemic mastocytosis, mast cells release more histamine than they should. Over time, these extra cells can build up in your skin, digestive system or other organs, causing symptoms that often look like an allergic reaction. Depending on where the cells gather, you may also have other symptoms, like stomach ulcers or bone pain.
There’s no cure for systemic mastocytosis, but treatments can help manage symptoms. In recent years, the FDA has also approved a handful of targeted therapies, with more on the horizon.
We spoke to Tracy George, MD, president of the Innovation Business Unit and chief scientific officer at ARUP Laboratories and professor of pathology at the Spencer Fox Eccles School of Medicine at the University of Utah, about why the condition is often tricky to diagnose, what people with systemic mastocytosis can expect from newer treatments, and more.
Who is most likely to get systemic mastocytosis?
Depending on the study, about 95% of patients who have systemic mastocytosis have an acquired mutation in the KIT gene [a gene that controls how certain cells develop, including mast cells]. The type of patient who develops the disease can vary depending on which form of disease they have. A recent study I presented found that patients with non-advanced systemic mastocytosis were mostly women with a median age of about 51 to 52. But when you look at patients with advanced disease — which is much rarer and has a worse prognosis — they tend to be older and are more likely to be men.
We still don’t know what risk factors predispose someone to get systemic mastocytosis, but we do know that it appears to be an acquired disease that primarily affects adults.
What are the key symptoms that distinguish systemic mastocytosis from allergies and other conditions?
You get a wide spectrum of different symptoms, including fatigue, gastrointestinal issues like nausea, vomiting, and diarrhea, and even anaphylaxis. More than 50% of patients with indolent systemic mastocytosis (ISM) — the most common form of the disease — develop skin lesions, which appear as flat, raised, red-brown itchy bumps. Some patients have neurological symptoms, like brain fog, while others may have joint pain. Having too many mast cells can also cause organ enlargement.
Because the symptoms are so varied, the condition can be difficult to diagnose. One study found that, on average, it took patients six to seven years to get a diagnosis. If you’re having symptoms, it’s important to go to a doctor to figure out what might be going on.
Are there any emerging diagnostic technologies on the horizon that might change patient care?
We can now detect the mutation in most patients through a blood draw. In patients with ISM especially, the mutation tends to be present at a low level, so you need to do sensitive testing. This can be a useful screening tool when combined with a serum tryptase test, which measures tryptase, a chemical secreted by mast cells.
More recently, data from Spain has highlighted a super-sensitive detection method. My lab is working on developing this method for detecting the mutation in peripheral blood so that we can offer it commercially to patients in the future.
How can patients best prepare for or avoid triggers that might make their symptoms worse?
There are avoidant things people can do: venom immunotherapy for those who have severe reactions to insect stings, avoiding certain trigger foods if you have gastrointestinal symptoms, or taking lukewarm showers if you have skin lesions.
After getting a diagnosis, some patients avoid social interactions. They may call in sick work or skip going to the beach because they’re embarrassed to put on a swimsuit. But nowadays, we have new effective disease-modifying treatments. Patients don’t have to suffer anymore thinking, “Well, I’m just going to have to live my life like this — I can never go outside or never leave my house.”
What do you see as the most exciting areas of research or innovation for systemic mastocytosis?
I’ve seen this go from a disease that was essentially untreatable to one that now has real treatment options for patients. That is super exciting.
Patients can take medications like antihistamines or cromolyn, which help stabilize mast cells so they don’t degranulate. While these treatments can manage symptoms, they don’t eliminate the disease. Fortunately, we now have drugs that specifically target the mutated KIT protein — like avapritinib and midostaurin — which are approved for patients with advanced systemic mastocytosis. With these drugs, the mast cell burden goes down, the mast cells change back to a normal shape, and their phenotype — the proteins they express in the surface — normalize. Patients objectively have fewer symptoms and feel better: Their spots go away, their bone pain reduces, they’re able to think clearly, and they have fewer anaphylactic episodes.
Other research shows that about 30% of patients with non-advanced systemic mastocytosis have osteoporosis or osteopenia. Emerging data shows that even after just one year of therapy on avapritinib, bone densities in these patients actually improves. These are outcomes we didn’t think we’d be able to change before.
What other new treatments are currently in development?
We recently got breakthrough designation for the drug bezuclastinib. It’s not approved yet, but we’re anticipating that it will be soon because the results look very promising. One of the most common side effects of avapritinib is swelling, especially in the face and around the eyes. There have also been reports of cognitive changes because the drug crosses the blood-brain barrier. What’s encouraging about bezuclastinib is that it appears to have less off-target effects — especially cognitive ones, since it doesn’t cross the blood-brain barrier. This means fewer side effects for patients.
Where should patients turn if they need more information or support?
I always encourage them to reach out to the patient advocacy societies in their country because they can offer a lot of additional support. In the United States, for example, we have the Mast Cell Disease Society.
One of the things we’ve heard from patients, loud and clear, is that there aren’t enough doctors who understand the disease and that many people don’t know where to go for care. In 2019, we started the American Initiative in Mast Cell Diseases (AIM). We now have 30 reference centers and centers of excellence where patients can get information or see an expert in their area. We still don’t have enough physicians and health care providers overall, but we’re in a much better place than we were.
What does the future look like for patients living with systemic mastocytosis?
We’re reaching the point where we might be able to eliminate the abnormal mast cells in some patients’ organs — and then we can start talking about a cure.
There’s never been a better time to be both a researcher and a patient.
