Treatment with the multityrosine kinase inhibitor pacritinib resulted in a significant reduction in spleen volume compared with best available therapy, including ruxolitinib, in patients with myelofibrosis and thrombocytopenia, according to a study presented at the American Society of Hematology (ASH) 58th Annual Meeting & Exposition.

For the phase 3 PERSIST-2 study ( identifier: NCT02055781), investigators enrolled 311 patients with primary, postpolycythemia, or postessential thrombocythemia myelofibrosis and platelet counts no greater than 100,000/µL. Participants were randomly assigned to receive pacritinib 200 mg orally twice daily, pacritinib 400 mg orally once daily, or best available therapy, including ruxolitinib.

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Results showed that 18% of the 149 patients who received pacritinib achieved a spleen volume reduction of 35% or greater by week 24 compared with 3% of the 72 patients who received best available therapy (P =.001), thus meeting the study’s first coprimary end point.

There was no significant difference in the proportion of patients achieving a 50% or greater reduction in Total Symptom Score, the study’s second co-primary end point, between the 2 groups. There was also no significant difference in overall survival between the 3 treatment groups.

Secondary analyses demonstrated that patients who received the twice-daily dosing of pacritinib achieved both a significant spleen volume reduction (22% vs 3%; P =.001) and a significant Total Symptom Score reduction (32% vs 14%; P =.011) vs best available therapy, suggesting pacritinib may be more active when administered twice daily.

The most common treatment-emergent adverse events with pacritinib were diarrhea, nausea, vomiting, anemia, and thrombocytopenia. Toxicities appeared to occur less frequently with the twice-daily dosing compared with once-daily administration.

Because of concerns about treatment-related deaths and cardiac and hematologic toxicities, the US Food and Drug Administration implemented a full clinical hold on pacritinib in February 2016; however, the administration removed the hold in January 2017, allowing CTI BioPharma, the drug’s developer, to continue investigation of pacritinib in patients with this myeloproliferative neoplasm.


1. Mascarenhas J, Hoffman R, Talpaz M, et al. Results of the Persist-2 Phase 3 Study of Pacritinib (PAC) Versus Best Available Therapy (BAT), Including Ruxolitinib (RUX), in Patients (pts) with Myelofibrosis (MF) and Platelet Counts <100,000/µL. Paper presented at American Society of Hematology (ASH) 58th Annual Meeting & Exposition; December 3-6, 2016; San Diego, CA.