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JAMA Oncol. 2018 May 1;4(5):652-659. doi: 10.1001/jamaoncol.2017.5818.

Pacritinib vs Best Available Therapy, Including Ruxolitinib, in Patients With Myelofibrosis: A Randomized Clinical Trial.

Author information

1
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
2
University of Michigan, Comprehensive Cancer Center, Ann Arbor.
3
Cleveland Clinic, Cleveland, Ohio.
4
Northwestern University, Feinberg School of Medicine, Chicago, Illinois.
5
Princess Margaret Cancer Center, University of Toronto, Ontario, Canada.
6
Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary.
7
Beatson West of Scotland Cancer Centre, Glasgow, Scotland.
8
Ryazan's Clinical Hospital, Ryazan, Russia.
9
CTI BioPharma Corp, Seattle, Washington.
10
Stanford University School of Medicine/Stanford Cancer Institute, Stanford, California.
11
University of California-San Diego, La Jolla.
12
Guy's and St Thomas' NHS Foundation Trust, London, England.
13
Mayo Clinic, Scottsdale, Arizona.
14
MD Anderson Cancer Center, Houston, Texas.

Abstract

Importance:

Myelofibrosis is a hematologic malignancy characterized by splenomegaly and debilitating symptoms. Thrombocytopenia is a poor prognostic feature and limits use of Janus kinase 1 (JAK1)/Janus kinase 2 (JAK2) inhibitor ruxolitinib.

Objective:

To compare the efficacy and safety of JAK2 inhibitor pacritinib with that of best available therapy (BAT), including ruxolitinib, in patients with myelofibrosis and thrombocytopenia.

Design, Setting, and Participants:

For this phase 3 randomized international multicenter study-the PERSIST-2 study-of pacritinib vs BAT, 311 patients with myelofibrosis and platelet count 100 × 109/L or less were recruited for analysis. Crossover from BAT was allowed after week 24 or for progression of splenomegaly.

Interventions:

Patients were randomized 1:1:1 to pacritinib 400 mg once daily, pacritinib 200 mg twice daily, or BAT.

Main Outcomes and Measures:

Coprimary end points were rates of patients achieving 35% or more spleen volume reduction (SVR) and 50% or more reduction in total symptom score (TSS) at week 24. Efficacy analyses were performed on the intention-to-treat efficacy population, comprising all patients with a randomization date allowing for week 24 data.

Results:

Overall, 311 patients (mean [SD] age, 63.70 [9.08] years; 171 men [55%] and 140 women [45%]) were included in the study; 149 patients (48%) had prior ruxolitinib. The most common BAT was ruxolitinib (44 patients [45%]); 19 patients (19%) received watchful-waiting only. The intention-to-treat efficacy population included 75 patients randomized to pacritinib once daily; 74, pacritinib twice daily, and 72, BAT. Pacritinib (arms combined) was more effective than BAT for 35% or more SVR (27 patients [18%] vs 2 patients [3%]; P = .001) and had a nonsignificantly greater rate of 50% or more reduction in TSS (37 patients [25%] vs 10 patients [14%]; P = .08). Pacritinib twice daily led to significant improvements in both end points over BAT (≥35% SVR: 16 patients [22%] vs 2 patients [3%]; P = .001; ≥50% reduction in TSS: 24 patients [32%] vs 10 patients [14%]; P = .01). Clinical improvement in hemoglobin and reduction in transfusion burden were greatest with pacritinib twice daily. For pacritinib once daily, pacritinib twice daily, and BAT, the most common (>10%) grade 3 or 4 adverse events were thrombocytopenia (32 patients [31%], 34 patients [32%], 18 patients [18%]), and anemia (28 patients [27%], 23 patients [22%], 14 patients [14%]). In the pacritinib once daily, twice daily, and BAT arms, discontinuation owing to adverse events occurred in 15 patients (14%), 10 patients (9%), and 4 patients (4%).

Conclusions and Relevance:

In patients with myelofibrosis and thrombocytopenia, including those with prior anti-JAK therapy, pacritinib twice daily was more effective than BAT, including ruxolitinib, for reducing splenomegaly and symptoms.

Trial Registration:

clinicaltrials.gov Identifier: NCT02055781.

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