Alternative Ruxolitinib Dosing Regimen May Mitigate Anemia in Patients With Myelofibrosis

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A recent open-label, single-arm, phase 2 study sought to assess evaluate an alternative dosing regimen for adults myelofibrosis (MF) to assess whether such a regimen could mitigate anemia.

While ruxolitinib is approved for twice-daily dosing to treat intermediate- or high-risk myelofibrosis (MF), anemia has been reported as an adverse event (AE) in more than 40% of patients in some clinical trials. Anemia in the early weeks of therapy may lead to treatment discontinuation, potentially leading to disease rebound.

A recent open-label, single-arm, phase 2 study sought to assess evaluate an alternative dosing regimen for adults with primary MF, postpolycythemia vera MF, or postessential thrombocythemia MF.

A total of 42 patients completed the study, and 37 completed a follow-up period. While prior therapies for MF were allowed, patients were required to discontinue all drugs to treat underlying MF before initiating ruxolitinib.


Patients were given ruxolitinib in oral doses of 5 mg tablets for 24 weeks. The starting dose for all patients was 10 mg twice per day, taken 12 hours apart. At weeks 12 and 18, doses could be increased by 5 mg twice per day in patients with lack of efficacy, and at any point, doses could be reduced for safety; if anemia was observed, doses could be dropped to 5 mg twice per day.

The study’s primary endpoint was the mean percentage change from baseline in spleen volume at week 24. Symptom severity was measured by the Myelofibrosis Symptom Assessment Form Total Symptom Score (MFSAF TSS).

The mean percentage reduction from baseline in spleen volume at weeks 12 and 24 was 16.3% (standard deviation [SD],12.4%) and 14.9% (SD, 21.1%), respectively.A dose-response relationship was observed, with week 24 mean spleen volume reductions of 20.1% (SD, 18.3%) and 32.9% (SD, 12.9%) among patients receiving average total daily doses of ruxolitinib or greater than 20 mg-30 mg and greater than 30mg-40 mg, respectively.

The mean baseline MFSAF TSS score was 16.6 (SD, 10.1), and this scored dropped with treatment; the mean score at weeks 6, 12, 18, and 24 was 10.5 (SD, 7.2), 10.0 (SD, 7.6), 8.4 (SD, 6.4), and 9.3 (SD, 8.0), respectively. At week 24, patients who were taking an average daily dose of more than  30 mg-40 mg had the greatest median percentage reduction from baseline in MFSAF TSSscore.

IN total, 93.3% of patients (n = 42) had a treatment-emergent AE. Anemia (26.7%) was the most commonly reported, followed by fatigue (22.2%) and arthralgia (20.0%). Seventeen patients (37.8%) had an AE of grade 3 or higher. One AE, myelodysplastic syndrome, led to treatment discontinuation and later death, and serious AEs were reported in 2 patients.

The authors concluded that, while treatment guidelines adhere to ruxolitinib’s dosing as described in its product label, dose escalation may be a feasible strategy for patients who have anemia or are likely to become anemic.


Talpaz M, Erickson-Viltanen S, Hou K, Hamburg S, Baer MR. Evaluation of an alternative ruxolitinib dosing regimen in patients with myelofibrosis: an open-label phase 2 study. J Hematolol Oncol. 2018; 11(1):101. doi: 10.1186/s13045-018-0642-0.