Phase III PERSIST-2 study: Post hoc analysis of pacritinib vs ruxolitinib in MF and thrombocytopenia

Results from a post hoc analysis of the phase III PERSIST-2 study (NCT02055781), evaluating pacritinib vs best available therapy (BAT) in patients with myelofibrosis (MF) and thrombocytopenia (platelet count ≤100 × 10⁹/L), were published in JCO Oncology Advances by Harrison et al. In PERSIST-2, patients were randomized 1:1:1 to receive pacritinib 200 mg twice daily (BID), pacritinib 400 mg once daily (QD), or BAT, defined as any MF therapy, including ruxolitinib alone or in combination regimens, either continuously or intermittently. The co-primary endpoints were the proportion of patients achieving ≥35% reduction in spleen volume (SV) and ≥50% reduction in Total Symptom Score (TSS) from baseline to Week 24. This analysis compared outcomes in patients assigned to pacritinib 200 mg BID (n = 106) vs patients assigned to BAT who received ruxolitinib at any time before Week 24 (n = 44). 

Key data: Most patients receiving ruxolitinib were treated at low doses (total daily dose [TDD] ≤10 mg), while most patients receiving pacritinib maintained the full TDD of 400 mg. In the intention-to-treat (ITT) population (pacritinib, n = 74; ruxolitinib as BAT, n = 32), pacritinib demonstrated higher SV response rates vs ruxolitinib (22% vs 3%; unadjusted p = 0.02; p = 0.06), numerically higher modified TSS (mTSS) response rates (35% vs 19%; unadjusted p = 0.11; p = 0.13), and greater transfusion independence (TI) rates in patients without red blood cell (RBC) TI at baseline (36.6% vs 5.6%; p = 0.02). Patient Global Impression of Change (PGIC) at Week 24 was numerically higher in patients receiving pacritinib vs ruxolitinib as BAT (35% vs 16%; p = 0.06). Overall rates of adverse events (AEs) were similar between pacritinib and ruxolitinib (94% vs 93%), though the incidence of fatal events was lower with pacritinib (8% vs 11%). Rates of any-grade infections (48% vs 27%), diarrhea (48% vs 16%), nausea (32% vs 16%), and Grade ≥3 bleeding events (16% vs 7%) were higher with pacritinib vs ruxolitinib.

Key learning: In this post hoc analysis of the PERSIST-2 study, pacritinib was associated with improved spleen, symptom, and anemia outcomes vs low-dose ruxolitinib in patients with MF and thrombocytopenia, supporting its use in this high-risk population.