Reanalysis Confirms Benefit of Fedratinib in MF Patients after Ruxolitinib Failure

By Annette M. Boyle, /alert Contributor
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Only one drug, the JAK2 inhibitor ruxolitinib, has received U.S. Food and Drug Administration approval for treatment of myelofibrosis, a life-threatening myeloproliferative neoplasm. Patients who experience relapse or become refractory or intolerant of that drug currently have few options.

New research presented at the American Society of Clinical Oncology Annual Meeting in Chicago provides hope that a second-line medication may be on the horizon.


Myelofibrosis diagnosis. Source: Getty

Researchers led by Claire N. Harrison, MD, of Guy’s and St. Thomas’ HS Foundation Trust in London found that another selective oral JAK2 inhibitor, fedratinib, that acts against both mutant JAK2 and wt reduced splenomegaly and symptom burden in patients determined to be resistant/refractory or intolerant of ruxolitinib. This study reanalyzed results of the previously released JAKARTA-2 study using substantially more rigorous definitions of relapse, refractory disease and intolerance to ruxolitinib to confirm that earlier findings of positive outcomes were due to the unique properties of fedratinib.

The stricter definition of relapse called for treatment with ruxolitinib for three months or longer with less than 10% reduction in spleen volume or less than 30% reduction in spleen size from baseline following initial response. The reanalysis considered patients refractory if they did not achieve 10% reduction in spleen volume or 30% reduction in spleen size for baseline (with no initial response.) The previous definition required 14 days of ruxolitinib treatment with no response or stable disease progression or loss of response, as determined by the study investigator.

The definition of intolerance changed from 14 days or longer on ruxolitinib therapy before discontinuation for unacceptable toxicity to 28 days or more of therapy, complicated by development of the need for red blood cell transfusion at least twice a month for at least two months or grade 3 or higher thrombocytopenia, anemia, hemorrhage or hematoma during therapy.

Using the new definitions reduced the number of patients in this second analysis to 79 from 97. At baseline, patients had a mean spleen volume about 14 times normal or 2946 mL. The median duration of ruxolitinib therapy was 11.5 months. Participants received fedratinib for an average of seven cycles.

Patients who met the more stringent definitions still achieved meaningful reductions in both spleen volume and symptoms with fedratinib. Spleen volume response rate was 30% with fedratinib and the symptom response rate was 27%. Duration of the spleen response was not estimable at the time of data closure (95% CI, 7.2 months-NE).


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