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JAK inhibitor provides rapid, durable relief for myelofibrosis patients
Date:9/15/2010

, a JAK1 and JAK2 inhibitor developed by Incyte Corp., established maximum tolerated doses and then optimal dosing regimens for the drug, which targets abnormal signaling caused by a specific mutation in the JAK2 gene that was discovered in 2005 in patients with myelofibrosis.

The clinical trial began in June 2007 at MD Anderson and the Mayo Clinic and enrolled 153 patients, all of whom had either advanced disease or were newly diagnosed with high intermediate- or high-risk myelofibrosis. Clinical responses have been maintained and 115 patients (75 percent) remain on the trial.

Most patients benefited, with those on optimal doses experiencing:

  • A median reduction in spleen volume, as measured by magnetic resonance imaging, of 33 percent at six months, with 48 percent enjoying reductions of 35 percent or higher. This equals a median reduction of 52 percent in the length of the spleen below the ribcage, measured by palpation, which is how spleen size is typically measured in clinical practice.
  • Swift and lasting spleen reduction; 70 percent to 82 percent of patients on the three optimal dosing regimens had spleen reduction of at least 25 percent that occurred within the first two months of therapy and lasted beyond a year.
  • Rapid and lasting improvement in symptom score, with 51 percent of patients achieving a 50 percent reduction at one month, and 58 percent maintaining that reduction at six months.
  • Greater exercise capacity as 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 ranging from 14.5 pounds to 20.6 lbs after one year.

Symptom improvement coincided with a quick and sustained reduction in a variety of inflammatory cytokines involved in disease biology.

The main side effect is lowered blood cell counts in some patients, which can be remedied by lower doses or temporarily
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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