Conference Coverage: Pacritinib Leads to Better Symptom Control, Improved Cytopenias in Myelofibrosis

CHICAGO—Compared to currently available treatments, the JAK2 inhibitor pacritinib led 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 ASCO meeting.

“Patients with myelofibrosis can have difficult symptoms which 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 which 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 patients 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. Researchers excluded ruxolitinib as a treatment due to the risks associated with its use among patients with low platelet counts.

“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. (Watch the full interview here.) “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 BAT arm.

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

  • 1 percent versus 4.7 percent for BAT (p=0.0003) in the intent-to-treat population
  • 25 percent versus 5.9 percent (p=0.0001) in the evaluable population

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

  • 5 percent versus 6.5 percent for BAT (p<0.0001) in the intent-to-treat population
  • 9 percent vs. 9.9 percent 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).

TABLE. Reduction in spleen volume (pacritinib vs. best available treatment), according to baseline cytopenia level

<100,000 μ/L

50,000 μ/L


Best available treatment p Value Pacritinib Best available treatment

p Value

Intent-to-treat population


0% 0.009 22.9% 0%


Evaluable population


0% 0.007 33.3% 0%


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.

Source: 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.