Results of the PERSIST-1 phase III study of pacritinib (PAC) versus best available therapy (BAT) in primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), or post-essential thrombocythemia-myelofibrosis (PET-MF).

Leukemia, Myelodysplasia, and Transplantation
Session Type and Session Title: 
Oral Abstract Session, Leukemia, Myelodysplasia, and Transplantation
Abstract Number: 


J Clin Oncol 33, 2015 (suppl; abstr LBA7006)
Ruben A. Mesa, Miklos Egyed, Anita Szoke, Aleksandr Suvorov, Andrew Perkins, Jiri Mayer, Peter Ganly, Eric Jourdan, Harry C. Schouten, Patrizia Tosi, Charles Michael Farber, Pierre Zachee, Christof Scheid, James P. Dean, Paul Cernohous, Jyoti Nangalia, Jean-Jacques Kiladjian, Alessandro M. Vannucchi, Adam Mead, Claire N. Harrison; Mayo Clinic Cancer Center, Scottsdale, AZ; Kaposi Mor Teaching Hospital, Kaposvar, Hungary; Universisty of Szeged, Szeged, Hungary; First Republican Clinical Hospital of Udmurtia, Izhevsk, Russia; Chermside Medical Centre, Chermside, Australia; Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic; Department of Haematology, Christchurch Hospital, Christchurch, New Zealand; Centre Hospitalier Universitaire de Nîmes, Nîmes, France; University Hosp Maastricht, Maastricht, Netherlands; Ospedale "Infermi", Rimini, Rimini, Italy; Morristown Memorial Hospital, Carol G. Simon Cancer Center, Morristown, NJ; ZNA Stuivenberg, Antwerp, Belgium; University of Cologne, Cologne, Germany; CTI BioPharma Corp., Seattle, WA; CTI BioPharma Corp, Seattle, WA; Cambridge Institute for Medical Research, Cambridge, United Kingdom; Hôpital Saint-Louis and Paris Diderot University, Paris, France; University of Florence, Florence, Italy; Oxford University Hospitals, Oxford, United Kingdom; Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom

Abstract Disclosures


Background: PAC is a potent JAK2 inhibitor without significant JAK1 inhibition with minimal myelosuppression in early-phase studies in MF. Methods: The efficacy and safety of daily oral PAC was compared to BAT (2:1 randomization stratified for risk and platelet count). The 10 endpoint was the proportion of ITT patients (pts) achieving ≥ 35% spleen volume reduction (SVR) at week (wk) 24 by centrally reviewed MRI or CT. Secondary endpoints included the proportion achieving ≥ 50% reduction in total symptom score (TSS) at wk 24 using the MPN Symptom Assessment Form. Results: Patients:327 were enrolled (PAC:220, BAT:107), 62% with 10 MF. Median time from diagnosis was 1.12 years (PAC 0.99, BAT 1.60): 32% and 15% had a platelet counts < 100,000/µL or <50,000/ µL; 75% were JAK2V617F positive. Efficacy: The median duration of treatment was 16.2 months PAC and 5.9 months BAT. Sixty-two percent of BAT patients received active disease directed therapy. The SVR rates at week 24 were 19.1% for PAC vs. 4.7% for BAT (p=0.0003) in ITT and 25% vs. 5.9% (p=0.0001) in the evaluable population. 79% of BAT patients crossed over to PAC; 21% had achieved a >35% reduction in spleen volume at data cutoff. TSS composite V1 + V2 response rates were 24.5%for PAC vs. 6.5% for BAT (p<0.0001) by ITT, and were 40.9% vs. 9.9% in evaluable pts (p<0.0001). Efficacy with baseline cytopenias: In pts with <100,000 and <50,000 platelets/μ/L, the SVR rates were 16.7% for PAC vs. 0% for BAT (p=0.009), and 22.9% vs. 0% (p=0.045) by ITT and 23.5% vs. 0% (p=0.007) and 33.3% vs. 0% (p=0.037) in evaluable pts. In RBC transfusion dependent pts, 25.7% of PAC pts became RBC independent vs. 0% of BAT pts (p=0.043). Safety: The most common adverse events (AE) for PAC were diarrhea, nausea, and vomiting; (grade 3 were <5%, <1%, <1% respectively). Hematologic AEs were similar between PAC and BAT. Conclusions: This study demonstrated PAC was well tolerated and induced significant and sustained SVR and symptom control even in patients with severe thrombocytopenia. PAC therapy resulted in RBC transfusion independence in a significant proportion of pts. Clinical trial information: NCT01773187