Mascarenhas J, et al. - Pacritinib, a Janus kinase 2 (JAK2) inhibitor, was compared with the best available therapy (BAT), including ruxolitinib, in patients with myelofibrosis and thrombocytopenia. In this patient population including those with prior anti-JAK therapy, pacritinib vs BAT, including ruxolitinib, was shown to be more effective in reducing splenomegaly and symptoms when given twice daily.

• A total of 311 patients with myelofibrosis and platelet count 100 × 10⁹/L or less were analyzed in this phase 3 randomized international multicenter study—the PERSIST-2 study—of pacritinib vs BAT.
• Crossover from BAT was allowed after week 24 or for progression of splenomegaly.
• Random assignment (1:1:1) of patients to receive pacritinib 400 mg once daily, pacritinib 200 mg twice daily, or BAT, was done.
• Rates of patients achieving 35% or more spleen volume reduction (SVR) and 50% or more reduction in total symptom score (TSS) at week 24 were the coprimary end points.
• Researchers carried out efficacy analyses in the intention-to-treat efficacy population, comprising all patients with a randomization date allowing for week 24 data.

• This study included a total of 311 patients (mean [SD] age, 63.70 [9.08] years; 171 men [55%] and 140 women [45%]); 149 patients (48%) had prior ruxolitinib.
• Ruxolitinib was noted to be the most common BAT (44 patients [45%]); 19 patients (19%) received watchful-waiting only.
• A total of 75 patients were included in intention-to-treat efficacy population; these patients were randomized to pacritinib once daily; 74, pacritinib twice daily, and 72, BAT.
• Findings demonstrated the greater efficacy of pacritinib (arms combined) than BAT for 35% or more SVR (27 patients [18%] vs 2 patients [3%]; P=.001).
• Moreover, pacritinib had a nonsignificantly greater rate of 50% or more reduction in TSS (37 patients [25%] vs 10 patients [14%]; P=.08).
• Researchers noted that 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).
• Furthermore, pacritinib twice daily resulted in greatest clinical improvement in hemoglobin as well as reduction in transfusion burden.
• Data showed that the most common (>10%) grade 3 or 4 adverse events for pacritinib once daily, pacritinib twice daily, and BAT, included thrombocytopenia (32 patients [31%], 34 patients [32%], 18 patients [18%]), and anemia (28 patients [27%], 23 patients [22%], 14 patients [14%]).
• Additionally, it was noted that 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%).