Editor’s note: this article was updated to correct an error regarding the target of pacritinib.

Pacritinib, an oral JAK2 inhibitor, may improve outcomes among patients with myelofibrosis and thrombocytopenia regardless of prior JAK-inhibitor therapy, according to a study published in JAMA Oncology.1

Myelofibrosis, a hematologic malignancy characterized by dysregulated JAK signaling, frequently leads to splenomegaly and thrombocytopenia as the disease progresses. The median overall survival is about 6 years. Thrombocytopenia may, furthermore, emerge during treatment with ruxolitinib, a JAK1/2 inhibitor, limiting treatment options. Pacritinib has “negligible” activity against the JAK1 kinase, and may lead to spleen volume reduction (SVR) and an improved total symptom score (TSS) in patients with myelofibrosis and thrombocytopenia.

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For this randomized phase 3 trial (ClinicalTrials.gov Identifier: NCT02055781), researchers evaluated whether pacritinib would improve SVR and TSS compared with the best available therapy (BAT), including ruxolitinib.

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Three hundred and eleven patients were randomly assigned 1:1:1 to once-daily pacritinib (400 mg; 75 patients included in analysis), twice-daily pacritinib (200 mg per dose; 74 patients), or BAT (72 patients). The primary endpoints were 35% or greater SVR and 50% or greater improvement in TSS at week 24.

The mean age was 63.7 years, 149 patients had received prior ruxolitinib, and the most common treatments in the BAT arm were ruxolitinib (44 patients), hydroxyurea (19 patients), prednisone with or without prednisolone (19 patients), and watchful-waiting (19 patients).

The combined pacritinib arms had an improved 35% or greater SVR rate of 18% vs 3% in the BAT arm (P = .001) as well as an improved 50% or more TSS reduction rate (25% vs 14%, respectively; P = .08). The greatest improvement in hemoglobin and reduction in transfusion burden was seen in the twice-daily pacritinib arm.

Overall survival data did not reach significance and were reported in Supplement 1 of the online article.

Fourteen percent of patients in the once-daily pacritinib arm, 9% of patients in the twice-daily arm, and 4% of patients in the BAT arm discontinued therapy because of an adverse event.

The authors concluded that this study shows “the clinical benefit of pacritinib in patients with myelofibrosis and thrombocytopenia (platelet count ≤100 × 109/L), including those with prior JAK2 inhibitor therapy.”


  1. Mascarenhas J, Hoffman R, Talpaz M, et al. Pacritinib vs best available therapy, including ruxolitinib, in patients with myelofibrosis: a randomized clinical trial. JAMA Oncol. 2018 Mar 8. doi: 10.1001/jamaoncol.2017.5818 [Epub ahead of print]