New treatment for rare blood cancer

In 2015, Sally Worthen developed a persistent itchy rash on her thighs and torso

A dermatologist took a sample from one of her wounds and referred her to a local hematologist, who asked her for a bone marrow biopsy and further laboratory studies

"She was sad," Watson said

Watson had advanced systemic mastocytosis (SM) - a rare but deadly blood cancer with a life expectancy of less than a few years

Find a treatment option

"At the time, there was no FDA-approved treatment for Sally's type of disease," recalls Watson's husband, Bill, a medical products specialist, who is part of the Food and Drug Administration.

They learned of an international Phase II clinical trial of a drug called midostaurin in patients with advanced SM

Jason Gotlib, MD, professor of hematology at Stanford School of Medicine, oversaw the trial

Advanced SM is caused by the proliferation of a type of white blood cell called mast cells, which can be found in several organs, including the bone marrow, spleen, liver, gastrointestinal tract, lymph nodes, and skin

Sally and Bill Worthen Joachim Sabisch

People with SM experience flushing, itching, diarrhea, and in some cases, life-threatening allergic reactions

disease progression

When Worthen first visited Stanford's Gotlib in early 2017, she wasn't feeling well

"Overall, her quality of life was poor," Goldlib said

About 95 percent of advanced SM cases are caused by mutations in a protein called KIT, which drives the proliferation of mast cells

Although a drug called imatinib is approved for advanced SM, it is ineffective against the D816V mutation (although it may be useful in rare SM patients with normal KIT or other genetic mutations)

Gotlib advised Worthen to participate in a phase 1 clinical trial of a drug he leads called avapritinib, which works similarly to midostat but is unlikely to cause serious side effects because it only targets the KIT protein

"Sally lost 20 pounds; she couldn't eat any food," Bill Watson said
.
"We said we'd do anything
.
Try or die
.
"

"Avapritinib is more selective than midosalin," Gottlib said
.
"It is specifically designed to inhibit the KIT D816V mutation, with few other targets
.
Midosolin is a big step forward in treating advanced SM, but It also treats several other targets, and avatinib is more effective
.
"

Jason Gotlib

When Sally Worthen joined the avapritinib trial, she experienced a dramatic change
.
"Within a few months, her trypsin levels dropped like a stone," her husband said
.
"Her scars started to disappear, and she was eating again
.
" Worthen's bone marrow biopsy showed a rapid decrease in mast cells and a shrinking spleen
.

"I couldn't believe it; it was like a miracle," she said
.

"Sally was like other patients who experienced significant improvement," Gottlieb said
.
"Together, they charted the effect of the drug
.
"

Of the 53 patients with advanced SM evaluated in the EXPLORER trial, 75% benefited at least from the drug, and 36% achieved complete remission
.
The drug is not without side effects, which may include facial swelling, diarrhea, nausea and fatigue
.
Patients with low platelet counts are also at risk for intracranial hemorrhage
.

Interim results from a subsequent phase 2 clinical trial called PATHFINDER led to FDA approval of avapritinib in June 2021
.
Results from both trials were published simultaneously in the December issue of Nature Medicine
.
Goldlib is the senior author and lead author on both papers
.

"We now have two drugs approved for first-line treatment of advanced SM," Gotlib said
.
"This is a really good example of the effectiveness of targeted therapy for a rare disease, and I'm excited to see how it's improving the lives of these patients
.
"

The treatment allowed Worthen to get her life back, including riding again
.
She now relies on regular blood tests to make sure her disease has not returned
.
"Slowly, I got stronger and now I feel like I'm back to where I was before the illness," she said
.
"I feel very, very lucky and grateful
.
"