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.