Evaluation of an alternative ruxolitinib dosing regimen in patients with myelofibrosis: an open-label phase 2 study.
BACKGROUND
Ruxolitinib improves splenomegaly and symptoms in patients with intermediate-2 or high-risk myelofibrosis; however, nearly half develop grade 3/4 anemia and/or thrombocytopenia, necessitating dose reductions and/or transfusions. We report findings from an open-label phase 2 study exploring a dose-escalation strategy aimed at preserving clinical benefit while reducing hematological adverse events early in ruxolitinib treatment.


METHODS
Patients with myelofibrosis received ruxolitinib 10 mg twice daily (BID), with incremental increases of 5 mg BID at weeks 12 and 18 for lack of efficacy (maximum, 20 mg BID). Symptom severity was measured using the Myelofibrosis Symptom Assessment Form Total Symptom Score (MFSAF TSS).


RESULTS
Forty-five patients were enrolled, 68.9% of whom had a Dynamic International Prognostic Scoring System score of 1 to 2 (i.e., intermediate-1 disease risk). Median percentage change in spleen volume from baseline to week 24 was - 17.3% (≥ 10% reduction achieved by 26 patients [57.8%]), with a clear dose response. Median percentage change in MFSAF TSS from baseline at week 24 was - 45.6%, also with a dose response. The most frequent treatment-emergent adverse events were anemia (26.7%), fatigue (22.2%), and arthralgias (20.0%). Grade 3/4 anemia (20.0%) and dose decreases due to anemia (11.1%) or thrombocytopenia (6.7%) were infrequent.


CONCLUSIONS
A dose-escalation approach may mitigate worsening anemia during early ruxolitinib therapy in some patients with myelofibrosis.


TRIAL REGISTRATION
ClinicalTrials.gov identifier, NCT01445769 . Registered September 23, 2011.
['Talpaz|Moshe|M|', 'Erickson-Viitanen|Susan|S|', 'Hou|Kevin|K|', 'Hamburg|Solomon|S|', 'Baer|Maria R|MR|']
D000368:Aged D000369:Aged, 80 and over D005260:Female D006801:Humans D053612:Janus Kinases D008297:Male D008875:Middle Aged D009570:Nitriles D055728:Primary Myelofibrosis D011720:Pyrazoles D011743:Pyrimidines
Ruxolitinib Myelofibrosis Anemia Thrombocytopenia Transfusion Janus kinase