For Patient with Mastocytosis, Newly Approved Drug Makes a World of Difference

Jeffrey Borges was used to hearing that doctors had few good treatments for his mastocytosis.

He’d heard it when he was first diagnosed with the disease at age 16 and a course of antihistamines and ultraviolet light therapy had little effect on the rash that covered most of his body. He heard it in his early 30s, when he became anemic and was again prescribed antihistamines. And he heard it five years ago, when he experienced a sizable weight loss and alarmingly high levels of a telltale blood enzyme and underwent six months of chemotherapy to little avail.

So when he came to Dana-Farber, he may have been unprepared for the message from Daniel DeAngelo, MD, PhD, chief of the Division of Leukemia at Dana-Farber.

“He told me about a clinical trial of a new drug — avapritinib — that may be the best thing yet for patients with mastocytosis,” Borges relates.

It has been exactly that for Borges. Since joining the trial in 2018, he has seen his rash clear up for the first time in 20 years, the swelling in his legs diminish, and his weight and blood marker levels return to normal.

Jeffrey Borges.

The improvement experienced by Borges and many of the other patients in the trial convinced the U.S. Food and Drug Administration to approve avapritinib – marketed as AYVAKITTM – as standard therapy for patients with severe systemic mastocytosis. In that trial and an earlier, phase 1 trial, 57% of participants had a measurable response to the drug, with 28% experiencing complete remissions of the disease and another 28% experiencing partial remissions.

“Advanced systemic mastocytosis is a debilitating disease marked by extensive damage in multiple organ systems due to infiltration of mast cells, and new treatment options are urgently needed to address these life-threatening complications,” said DeAngelo, who led the phase 2 trial, dubbed PATHFINDER. “Avapritinib will clearly establish a new standard of care for patients with advanced systemic mastocytosis.”

Systemic mastocytosis is a rare disease caused by a buildup of mast cells — immune system cells normally found in connective tissue — in different parts of the body such as the skin, bone marrow, and digestive tract. Mast cells play a role in allergic reactions. When they’re triggered in a person with mastocytosis, the result can be severe inflammation and, potentially, damage to the affected organ or tissue. Traditionally, treatment options have been limited to antihistamines, antacids for digestive discomfort, and corticosteroids.

Avapritinib is a targeted medicine that works by blocking an abnormal form of the KIT protein, which is an enzyme that signals mast cells to proliferate.

‘Like night and day

For Borges, who lives in Little Compton, R.I., avapritinib has been a departure from previous therapies that promised little — and delivered on that promise. He began by taking three pills a day and saw his rash — which he describes as looking like “a million little freckles” — begin to diminish, his swelling go down, and his anemia begin to improve. Because he often felt nauseous in the morning, he reduced his intake to two pills a day, which alleviated the problem.

Today, his rash has vanished and his levels of tryptase — a blood enzyme used to track the proliferation of mast cells — has fallen from 350 to one. (Anything under 14 is considered normal.) His spleen, which had swollen and was “hard as a rock” has softened and shrunk back to almost normal, Borges says. Where he once needed almost daily transfusions, he hasn’t required one in over a year. The swelling in his legs that sometimes left him unable to work has eased, although it still flares up after a long day on his feet.

“Compared to how I used to feel, it’s like night and day,” Borges remarks. “It’s amazing.”