Pacritinib vs Best Available Therapy, Including Ruxolitinib, in Patients With Myelofibrosis A Randomized Clinical Trial JAMA ONCOLOGY Mascarenhas, J., Hoffman, R., Talpaz, M., Gerds, A. T., Stein, B., Gupta, V., Szoke, A., Drummond, M., Pristupa, A., Granston, T., Daly, R., Al-Fayoumi, S., Callahan, J. A., Singer, J. W., Gotlib, J., Jamieson, C., Harrison, C., Mesa, R., Verstovsek, S. 2018; 4 (5): 652–59

Abstract

Myelofibrosis is a hematologic malignancy characterized by splenomegaly and debilitating symptoms. Thrombocytopenia is a poor prognostic feature and limits use of Janus kinase 1 (JAK1)/Janus kinase 2 (JAK2) inhibitor ruxolitinib.To compare the efficacy and safety of JAK2 inhibitor pacritinib with that of best available therapy (BAT), including ruxolitinib, in patients with myelofibrosis and thrombocytopenia.For this phase 3 randomized international multicenter study-the PERSIST-2 study-of pacritinib vs BAT, 311 patients with myelofibrosis and platelet count 100?×?109/L or less were recruited for analysis. Crossover from BAT was allowed after week 24 or for progression of splenomegaly.Patients were randomized 1:1:1 to pacritinib 400 mg once daily, pacritinib 200 mg twice daily, or BAT.Coprimary end points were rates of patients achieving 35% or more spleen volume reduction (SVR) and 50% or more reduction in total symptom score (TSS) at week 24. Efficacy analyses were performed on the intention-to-treat efficacy population, comprising all patients with a randomization date allowing for week 24 data.Overall, 311 patients (mean [SD] age, 63.70 [9.08] years; 171 men [55%] and 140 women [45%]) were included in the study; 149 patients (48%) had prior ruxolitinib. The most common BAT was ruxolitinib (44 patients [45%]); 19 patients (19%) received watchful-waiting only. The intention-to-treat efficacy population included 75 patients randomized to pacritinib once daily; 74, pacritinib twice daily, and 72, BAT. Pacritinib (arms combined) was more effective than BAT for 35% or more SVR (27 patients [18%] vs 2 patients [3%]; P?=?.001) and had a nonsignificantly greater rate of 50% or more reduction in TSS (37 patients [25%] vs 10 patients [14%]; P?=?.08). 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). Clinical improvement in hemoglobin and reduction in transfusion burden were greatest with pacritinib twice daily. For pacritinib once daily, pacritinib twice daily, and BAT, the most common (>10%) grade 3 or 4 adverse events were thrombocytopenia (32 patients [31%], 34 patients [32%], 18 patients [18%]), and anemia (28 patients [27%], 23 patients [22%], 14 patients [14%]). 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%).In patients with myelofibrosis and thrombocytopenia, including those with prior anti-JAK therapy, pacritinib twice daily was more effective than BAT, including ruxolitinib, for reducing splenomegaly and symptoms.clinicaltrials.gov Identifier: NCT02055781.

View details for PubMedID 29522138

View details for PubMedCentralID PMC5885169