Pacritinib Leads to Better Symptom Control, Improved Cytopenias in Myelofibrosis

Compared with other available treatments, the JAK2 inhibitor pacritinib leads to more effective spleen volume reduction and better symptom control in patients with myelofibrosis, according to results of the phase III PERSIST-1 study presented at the 2015 American Society of Clinical Oncology meeting.

“Patients with myelofibrosis can have difficult symptoms that can have a significant negative impact on their quality of life,” Ruben A. Mesa, MD, professor of medicine at the Mayo Clinic in Scottsdale, Arizona, and the first author of the study said during a press conference. “In our therapies for myelofibrosis, we have not had agents that have been able to simultaneously improve splenomegaly symptoms from which patients suffer while also impacting, in a favorable way, their cytopenias.”

In PERSIST-1, Dr. Mesa and colleagues enrolled 327 patients (median time from diagnosis, 1.12 years) with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis. Thirty-two percent of patients had platelet counts <100,000 /µL, and 15 percent had platelet counts <50,000/µL.

Patients were randomly assigned 2:1 to receive either daily oral pacritinib (n=220) or best available treatment (n=107), which included erythropoietin-stimulating agents, immunomodulatory drugs, and hydroxyurea, though use of ruxolitinib was not allowed.

“One of the limitations of the only currently FDA-approved therapy, ruxolitinib, is that it is indicated in patients with a platelet count above 50,000/µL,” Dr. Mesa explained in an interview with ASH Clinical News.

“Many patients with very advanced disease have significant thrombocytopenia, and that is a limiter for ruxolitinib because the drug can cause thrombocytopenia.”

The primary endpoint was defined as spleen volume reduction (SVR) of ≥35 percent at 24 weeks in the intent-to-treat population. The median duration of treatment was 16.2 months in the pacritinib arm, versus 5.9 months in the best available therapy (BAT) arm.

At 24 weeks, the investigators observed a greater SVR reduction in the pacritinib group:

  • 19.1% vs. 4.7% for BAT (p=0.0003) in the intent-to-treat population
  • 25% vs. 5.9% (p=0.0001) in the evaluable population

Symptom control (a secondary endpoint defined as a 50% or greater reduction of total symptom score at 24 weeks) was also improved with pacritinib:

  • 24.5% vs. 6.5% for BAT (p<0.0001) in the intent-to-treat population
  • 40.9% vs. 9.9% in evaluable patients (p<0.0001)

At the time of data cut-off, 79 percent of BAT patients crossed over to pacritinib, while 21 percent had achieved a >35 percent SVR.

“The distinguishing characteristic of this study is that patients had no limitations on pre-existing platelet counts before entering the study,” Dr. Mesa said. While efficacy was seen in all of the subgroups analyzed in the study – regardless of platelet count – he also noted that there was significant treatment effect present in the highest-risk subset of patients (TABLE).

More red blood cell–dependent patients in the pacritinib arm also became transfusion-independent (25.7% vs. 0% of BAT patients; p=0.043).

Rates of adverse events were similar among all treatment types, with diarrhea, nausea, and vomiting as the most commonly reported adverse events among patients taking pacritinib.

“[The findings represent] an incremental benefit over our current landscape with [pacritinib] maintaining improvement in splenomegaly symptoms, which has been shown across the JAK2 inhibitor class, but also incremental benefit in improvement in cytopenias,” Dr. Mesa told ASH Clinical News.

Other trials to help identify the ideal patient population for pacritinib are currently underway, Dr. Mesa added, including the PERSIST-2 trial, which will examine the drug’s safety and efficacy exclusively in patients with thrombocytopenia.


Mesa RA, Egyed M, Szoke A, et al. 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). Abstract LBA7006. Presented at the 2015 American Society of Clinical Oncology Annual Meeting, Chicago, IL, May 30, 2015.

TABLE. Reduction in Spleen Volume (pacritinib vs. best available treatment), According to Baseline Cytopenia Level
<100,000 μ/L 50,000 μ/L
Pacritinib BAT p Value Pacritinib BAT p Value
Intent-to-treat population 16.7% 0% 0.009 22.9% 0% 0.045
Evaluable population 23.5% 0% 0.007 33.3% 0% 0.037