Mastocytosis is a rare, sometimes deadly, immune disorder that most people have never heard of.
It is a shapeshifter. With the indolent form of the disease, some people have mild symptoms and lead normal lives, while others may develop flushing, diarrhea and life-threatening anaphylactic shock. In advanced mastocytosis, sufferers develop mast cell leukemia, and most die within six months.
Now, a new drug tested at the UNM Comprehensive Cancer Center is showing promise to help those with advanced mastocytosis – and possibly many others. The drug, called midstaurin, extended the lives of those with advanced mastocytosis an average of 28 months longer than those receiving the current treatment.
“This is the first drug that’s shown to be effective in this very rare disease,” says Tracy George, MD, chief of UNM’s Division of Hematopathology and vice chair for clinical affairs in the Department of Pathology. She was part of an international team that recently published the results of its mastocytosis study in the New England Journal of Medicine.
“Mast cells are normal cells in the body that mediate the body’s allergic and inflammatory responses,” George explains. “But people with mast cell disease have too many mast cells and they’re abnormal.” These abnormal cells can cause allergic reactions and inflammation.
The Food and Drug Administration has approved only one drug, called imatinib, to treat advanced mastocytosis. It blocks the action of a cellular protein called a tyrosine kinase receptor. But most people with advanced mastocytosis have a mutation in a gene called D816V KIT and do not respond to imatinib, George says.
Research on the new treatment began at Stanford University, where George worked with a colleague, Jason Gotlib, MD, whose patient had mast cell leukemia. They gave that woman a midostaurin, a multi-kinase inhibitor, under the FDA’s compassionate use policy.
“Midostaurin was being evaluated in a clinical trial for a different disease, acute myeloid leukemia,” George says. “This lady with mast cell leukemia remarkably improved within weeks – within days.”
Gotlib and George began a small clinical trial to test midostaurin in people with advanced mastocystosis. Their efforts expanded into an international clinical trial after Gotlib and George shared their preliminary results at a conference. George brought the clinical trial with her when she joined UNM’s pathology department and the UNM Comprehensive Cancer Center.
The clinical trial included treatment for three subtypes of advanced mastocytosis, but it took years to enroll enough people because the disease is so rare. Mastocytosis affects only about one person in 10,000. In comparison, breast cancer affects more than 12 times as many people, according to the American Cancer Society.
People with advanced mastocytosis on the clinical trial lived an average of 28 months longer. This average includes the 40 percent of people who did not respond to midostaurin. The 60 percent who did respond did so within two or three months of starting treatment. They had mild side effects like diarrhea, vomiting and nausea, if they had any at all.
Sixteen people in the clinical trial had mast cell leukemia. “For those patients who did respond,” says George, “their median survival has not been reached. So that means [some are] still living, which is unbelievable.”
The clinical trial has spurred more research. Scientists around the world are now studying how midostaurin affects mast cells and how to combine it with other drugs to create an even more potent treatment.
Novartis, the maker of midostaurin, and other drug companies are researching other multi-kinase inhibitors. Clinical trials to test midostaurin for controlling symptoms in people with indolent mastocytosis are underway. And more research into using midostaurin to treat asthma, skin diseases and allergies is in the planning stages.
“I do think this is under-diagnosed,” says George, who is the American expert in the mastocytosis disease process. “Even though patients with advanced mastocytosis are rare, the indolent form is more common. And there are lots of cases in which unhappy mast cells cause disease.”
Now, with the potential for a treatment, people with unhappy mast cells may feel better.