Background
Phase 3 randomized trial of 311 patients with myelofibrosis and platelet count ≤100 x 10^9/L, comparing two pacritinib schedules vs best available therapy (BAT, including ruxolitinib). 149 patients (48%) had prior ruxolitinib. Crossover from BAT was allowed after week 24 or for splenomegaly progression.
Interventions and follow up
Arm A: Pacritinib 400 mg once daily
Arm B: Pacritinib 200 mg twice daily
Arm C: Best available therapy (including approved JAK2 inhibitors)
Primary endpoints: Spleen volume reduction (SVR) ≥35% and ≥50% reduction in Total Symptom Score (TSS) at 24 weeks
Arm B: Pacritinib 200 mg twice daily
Arm C: Best available therapy (including approved JAK2 inhibitors)
Primary endpoints: Spleen volume reduction (SVR) ≥35% and ≥50% reduction in Total Symptom Score (TSS) at 24 weeks
Results
SVR ≥35% at 24 weeks: 14.7% (Arm A) vs 21.6% (Arm B) vs 2.8% (BAT)
≥50% TSS reduction: 17.3% vs 32.4% vs 13.9%, P=.08
Pooled pacritinib (A+B) vs BAT — SVR ≥35%: 22% vs 3%, P=.001
Pooled pacritinib (A+B) vs BAT — ≥50% TSS reduction: 32% vs 14%, P=.01
≥50% TSS reduction: 17.3% vs 32.4% vs 13.9%, P=.08
Pooled pacritinib (A+B) vs BAT — SVR ≥35%: 22% vs 3%, P=.001
Pooled pacritinib (A+B) vs BAT — ≥50% TSS reduction: 32% vs 14%, P=.01
Adverse events
Hematologic (grade 3-4): Thrombocytopenia 31% (Arm A) vs 32% (Arm B) vs 18% (BAT); anemia 27% vs 22% vs 14%
Gastrointestinal/other: Diarrhea 48% and nausea 32% (most common with pacritinib); discontinuation for adverse events 14% vs 9% vs 4%
Gastrointestinal/other: Diarrhea 48% and nausea 32% (most common with pacritinib); discontinuation for adverse events 14% vs 9% vs 4%
Conclusions
Despite truncation by a clinical hold that compromised the week-24 analysis, PERSIST-2 demonstrated superior spleen and symptom benefit of pacritinib over best available therapy in myelofibrosis with thrombocytopenia (platelets ≤100K), including patients with prior JAK2 inhibitor therapy.
Key Limitations
An FDA clinical hold for cardiac and bleeding signals truncated enrollment and follow-up, undermining the primary 24-week analysis. Open-label design with heterogeneous BAT. The approved 200 mg twice-daily schedule was identified post hoc.
Clinical Context
PERSIST-2 supported the FDA approval of pacritinib (200 mg twice daily) for myelofibrosis with severe thrombocytopenia (platelets <50K), addressing a population for whom ruxolitinib dosing is limited. Pacritinib is recognized for cytopenic myelofibrosis per ESMO guidance.