Ruxolitinib Versus Best Available Therapy for Essential Thrombocythemia

Treatment with the JAK1/2 inhibitor ruxolitinib failed to improve response rates, compared with best-available therapy (BAT) in patients with essential thrombocythemia (ET) who were intolerant or resistant to standard frontline treatment with low-dose aspirin and hydroxycarbamide, according to results from a randomized phase II trial published in Blood. However, ruxolitinib improved certain disease-related symptoms, including pruritus, concentration, and ability to perform daily activities, noted Claire N. Harrison, MD, from Guy’s and St. Thomas’ Hospital in London, United Kingdom, and co-authors.

The open-label, randomized, controlled MAJIC-ET trial included 116 adult patients from 31 U.K. centers (median age = 64.2 years; range = 34.5-90.5 years) with high-risk ET that was resistant to treatment with hydroxycarbamide. Six patients were excluded from the final analysis: four withdrew without treatment (2 refused to be in the BAT arm, 1 became ineligible, and 1 had transformed to post-ET myelofibrosis), and two did not start treatment within one year of randomization.

The remaining 110 patients were randomized to receive either:

  • ruxolitinib at a starting dose of 25 mg twice-daily (or 20 mg twice-daily if baseline platelets were 100-200×109/L; n=58)
  • BAT chosen by the physician (n=52)

Over a median follow-up of 2.61 years (range = 0.23-4.12 years), ruxolitinib-treated patients received a median dose of 19 mg twice-daily (range not provided), and the most commonly used treatments in the BAT arm were hydroxycarbamide (n=37), anagrelide (n=25), and interferon (n=21).

Thirty-five patients in the ruxolitinib group discontinued treatment, compared with nine patients in the BAT group. “However, 30 BAT patients switched their initially assigned BAT treatment for various reasons, which indicates a similar rate of treatment ineffectiveness or intolerance,” the authors wrote.

Rates of complete response (CR; primary outcome) at two-year follow-up were similar in the ruxolitinib and BAT groups (27 patients [46.5%] vs. 23 patients [44.2%], respectively; p=0.4). Rates of partial response (PR) were also similar between the two treatment groups: 27 (46.5%) versus 27 (51.9%), respectively. No baseline factors (including hydroxycarbamide resistance, platelet counts, or JAK2 status) influenced response rates in multivariate analyses.

Thirteen patients in the study transformed to post-ET myelofibrosis: eight in the ruxolitinib group and five in the BAT group. One ruxolitinib-treated patient transformed to acute myeloid leukemia (AML), and, again, transformation-free probability was not significantly different between the two arms (p=0.29).

Ruxolitinib treatment appeared to reduce patients’ symptom burden, according to an analysis of 85 patients (47 in the ruxolitinib group and 38 in the BAT group) who completed a total symptom score (TSS) assessment at baseline and at least once after baseline.

The overall symptom response rate (defined as a 50% reduction in TSS during the first 12 months of treatment) did not differ significantly between the ruxolitinib and BAT groups (12 [29%] vs. 6 [19%], respectively; p=0.37), but the magnitude of symptom reduction appeared to be greater in the ruxolitinib group (median reduction in TSS = 32% vs. 0%; p=0.03). Symptom response was “rapid” in the ruxolitinib arm, occurring within two months in eight patients (19%), compared with in one patient (3%) in the BAT group (p=0.04).

In the safety analysis, which included all 115 patients in the MAJIC-ET trial who received ruxolitinib or BAT, 128 grade 3/4 adverse events (AEs)
occurred in 89 patients, including:

  • grade 3/4 anemia: 12 patients (21%) in the ruxolitinib arm versus 0 in the BAT arm (p<0.005)
  • grade 3/4 thrombocytopenia: 2 patients (3.4%) versus 0 (p=0.32)
  • grade 3 infections: 9 patients (15.5%) versus 2 (3.5%; p=0.03)

There were five patient deaths in the ruxolitinib arm and two in the BAT arm, but none was considered treatment related.

Thrombotic events were more common in the ruxolitinib group than in the BAT group: 10 ruxolitinib-treated patients (17.2%) experienced 11 events, and three BAT patients (5.8%) experienced five events (p=0.09). Hemorrhagic events appeared to be more common in the BAT group (1 [1.7%] vs. 5 [8.9%]; p=0.14).

“Overall thrombosis, hemorrhage, or transformation considered separately or together as a composite endpoint were not statistically different between the ruxolitinib and BAT [cohorts],” the authors concluded.

The study’s findings are limited by the variation in treatment choice in the BAT group, and, the authors noted, “the use of hydroxycarbamide as a BAT and frequent switching of BAT therapies also reflect real-life constraints and limited treatment options” for this group of patients with high-risk ET.

Dr. Harrison reports financial relationships with Novartis, the manufacturer of ruxolitinib.  


Harrison CN, Mead AJ, Panchai A, et al. Ruxolitinib versus best available therapy for ET intolerant or resistant to hydroxycarbamide in a randomized trial. Blood. 2017 August 9. [Epub ahead of print]