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Optimal dose of JAK inhibitor demonstrated benefits in patients with myelofibrosis
51st ASH Annual Meeting
In patients with myelofibrosis, an optimized dosing regimen of INCB018424, an investigational oral selective inhibitor of the JAK 1 and 2 enzymes, showed clinical, symptomatic and functional benefits with an improved hematological safety profile compared with the previously studied 25 mg twice daily regimen.
“Because myelofibrosis is a disease for which there is no approved therapy at all, and which causes life expectancy to be short, five to seven years on average, the need for new effective therapies is high. It is therefore gratifying to see the JAK inhibitor provide meaningful clinical benefits to these underserved patients,” Srdan Verstovsek, MD, PhD, associate professor, department of leukemia, division of cancer medicine, at The University of Texas M.D. Anderson Cancer Center, told HemOnc Today.
Verstovsek presented preliminary findings at the 2008 ASH Annual Meeting that showed that INCB018424 may shrink enlarged spleens and improve other disease-related symptoms in patients with myelofibrosis.
In the current study analysis, patients with primary myelofibrosis or myelofibrosis occurring after polycythemia vera or essential thrombocythemia (n=153) were enrolled. They were assigned to an optimized dose of 10 mg, 15 mg or 25 mg of INCB018424 twice daily.
Researchers assessed efficacy using MRI measurements of spleen size at one, three and six months. They surveyed patients about their health and well-being to measure the effect of INCB018424 on myelofibrosis-related symptoms. Exercise capacity was measured using a standardized six-minute walk test at baseline and at one, three and six months.
When compared with a starting dose of 25 mg twice daily, an optimized dosing regimen with starting doses of 10 mg or 15 mg twice daily, and increased or decreased doses depending upon each patient’s needs, demonstrated improved quality of life and disease symptoms, reduction in spleen size and an improved hematologic safety profile.
Rapid reduction of spleen volume was noted as early as one month and lasted beyond six months of treatment. After six months, 48% of patients had decreased spleen volume of less than 35%.
Improvement was observed for the six-minute walk test with median increases of 33 meters at one month of therapy, 58 meters at three months and 70 meters at six months. There was an association between spleen response and greater improvement in exercise capacity and reduced fatigue, and a large majority of patients reported improved health and well-being with treatment.
“While the treatment approach for these patients has been mostly in the form of palliative care, INCB018424 may provide patients with the first-ever treatment option that is designed to work on the underlying cause of this disease,” Verstovsek said in a press release.
“The therapy is very effective in the majority of patients we have studied. The medication is currently being evaluated in two pivotal phase-3 studies for patients with myelofibrosis. These trials are being conducted all over the world and are the largest and most extensive trials we have ever conducted in myelofibrosis,” Verstovsek told HemOnc Today. - by Christen Haigh
For more information:
- Verstovsek S. #756. Presented at: 51st ASH Annual Meeting and Exposition, Dec. 4-8, 2009, New Orleans.
