Patients with myelofibrosis experienced relief from pain, fatigue, and other symptoms associated with enlarged spleens after treatment with a JAK1 and JAK2 inhibitor, according to study results from Houston’s M.D. Anderson Cancer Center.
“The problem with myelofibrosis is the lack of available therapies for patients; there are none approved for this disease today,” said principal investigator Srdan Verstovsek, MD, PhD, an associate professor in the department of leukemia. The average life expectancy for people with this disease is five to seven years. Available therapies approved for other diseases provide little response and are mainly palliative.
INCB018424 from Incyte targets abnormal signaling caused by a specific mutation in the JAK2 gene of patients with myelofibrosis. The phase I/II clinical trial established maximum tolerated doses and optimal dosing regimens for the drug.
The trial began in June 2007 at M.D. Anderson and at the Mayo Clinic in Rochester, Minn. One hundred fifty-three patients with advanced or newly diagnosed myelofibrosis were enrolled.
To date, clinical responses have been maintained in the 115 patients (75%) who remain on the trial (N Engl J Med 363:1117- 1127, 2010).
Based on MRI measurements, the patients also experienced a median reduction in spleen volume of 33% at six months, with nearly half the patients experiencing reductions of 35% or higher. This equaled a median reduction of 52% in the length of the spleen below the ribcage as measured by palpation.
In addition, there was a rapid and lasting improvement in symptom score, with more than half the patients achieving a 50% reduction at one month and 58% maintaining that reduction at six months. Greater exercise capacity was measured in a six-minute walk. Patients increased their distance by a median of 34 meters at one month and 71 meters at six months. Median weight gain ranged from 14.5 pounds to 20.6 pounds after one year.
“This experimental drug is the first to target one of the underlying abnormalities in the malignant cells that cause myelofibrosis,” Dr. Verstovsek said. “It provides unprecedented reduction of enlarged spleens that are a central characteristic of the disease, and relieves pain, fatigue and other symptoms, improving quality of life.”