Background
Phase 3 randomized trial of 327 patients with higher-risk myelofibrosis (primary, post-ET, or post-PV MF) and palpable splenomegaly (≥5 cm), comparing pacritinib vs best available therapy. 46% were thrombocytopenic (32% platelets <100K, 16% <50K).
Interventions and follow up
Arm A: Oral pacritinib 400 mg once daily (n=220)
Arm B: Best available therapy (physician-selected, excluding JAK2 inhibitors; n=107); 90 patients crossed over to pacritinib at a median of 6.3 months
Primary endpoint: Spleen volume reduction (SVR) ≥35% at 24 weeks
Median follow-up: 23.2 months
Arm B: Best available therapy (physician-selected, excluding JAK2 inhibitors; n=107); 90 patients crossed over to pacritinib at a median of 6.3 months
Primary endpoint: Spleen volume reduction (SVR) ≥35% at 24 weeks
Median follow-up: 23.2 months
Results
SVR ≥35% at 24 weeks: 19% (pacritinib) vs 5% (BAT), P=.0003
By subtype: Primary MF 19% vs 3%; secondary MF 19% vs 6%
Median duration of treatment: 15.6 months vs 5.9 months
Crossover responders: 12% achieved SVR after switching from BAT to pacritinib
By subtype: Primary MF 19% vs 3%; secondary MF 19% vs 6%
Median duration of treatment: 15.6 months vs 5.9 months
Crossover responders: 12% achieved SVR after switching from BAT to pacritinib
Adverse events
Hematologic (grade ≥3): Anemia 17% (pacritinib) vs 15% (BAT); thrombocytopenia 12% vs 11%
Other: Diarrhea 5% vs 0%; deaths due to adverse events 12% vs 13%
Other: Diarrhea 5% vs 0%; deaths due to adverse events 12% vs 13%
Conclusions
Pacritinib produced a significant improvement in spleen volume reduction over best available therapy and may be a treatment option for myelofibrosis, including patients with baseline cytopenias for whom JAK inhibitor options are limited.
Key Limitations
Open-label design with a heterogeneous BAT comparator. A subsequent FDA clinical hold for cardiac and bleeding safety signals interrupted the program. Symptom and survival endpoints were exploratory in this analysis.
Clinical Context
PERSIST-1, with PERSIST-2, supported the later FDA approval of pacritinib for myelofibrosis with severe thrombocytopenia (platelets <50K), a population underserved by ruxolitinib. Pacritinib is a recognized JAK2/IRAK1 inhibitor option for cytopenic myelofibrosis per ESMO guidance.