CHICAGO—The potent JAK2 inhibitor, pacritinib, induced significant and sustained spleen volume reduction (SVR) and symptom control in patients with myelofibrosis compared with best available therapy, even in those with severe thrombocytopenia, results of the phase 3 PERSIST-1 study concluded at the 2015 American Society of Clinical Oncology (ASCO) annual meeting in Chicago, IL.

In addition, treatment with pacritinib therapy resulted in red blood cell (RBC) transfusion independence in a significant proportion of patients, said Ruben A. Mesa, MD, Deputy Director of the Mayo Clinic Cancer Center in Scottsdale, AZ.

At 24 weeks of treatment, in the intent-to-treat population, 19.1% of patients on the pacritinib arm experienced SVR, compared with 4.7% of patients who received best available therapy (P=0.0003); in the evaluable population, these rates were 25% compared with 5.9%, respectively (P=0.0001).

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“There is a huge unmet clinical need for patients with myelofibrosis. Only one drug is currently FDA approved for the disease, and it is not safe for patients with low platelet counts,” said Dr. Mesa in a press release.

As early as 1 year from the time of diagnosis, he explained, incidence of disease-related thrombocytopenia, anemia, and RBC transfusion requirements increase dramatically, with thrombocytopenia being a prognostic factor both for shorter overall survival and risk of leukemic transformation.

A total of 327 patients with a diagnosis of myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia-myelofibrosis  were enrolled and randomly assigned 2:1, stratified for risk and platelet count, to daily oral pacritinib (220 patients) or best available therapy (107 patients).

Best available therapy was primarily hydroxycarbamide (55.7%); other agents included prednisone, interferon alfa, thalidomide, danazol, prednisolone, busulfan, cytarabine, and peginterferon alfa-2a.

The end point was the proportion of patients achieving 35% or higher SVR at week 24 by centrally reviewed MRI or CT. Secondary end points included the proportion achieving 50% or greater reduction in total symptom score from baseline to week 24 using the Myeloproliferative Neoplasm (MPN) Symptom Assessment Form.

Among patients in the best available therapy arm, 79% crossed over to pacritinib and 21% had achieved a 35% or higher SVR at data cutoff.

Total symptom score composite response rates were 24.5% for pacritinib compared to 6.5% for best available therapy (P<0.0001) in the intent-to-treat population and 40.9% compared to 9.9%, respectively, in the evaluable patients (P<0.0001).

Patients with baseline platelets less than 50,000/µL had mean increase in platelet counts of 35% by week 24. In RBC transfusion-dependent patients, 25.7% of patients in the pacritinib arm became RBC independent compared with 0% of those receiving best available therapy (P=0.043).

The most common adverse events (AE) for pacritinib were diarrhea (grade 3, 5%), nausea (grade 3, 0.9%), and vomiting (grade 3, 0.9%). Hematologic AEs were similar between the pacritinib and best available therapy arms. The symptoms typically lasted less than 1 week and few patients discontinued treatment due to side effects.

Longer follow up is needed to determine if pacritinib improves survival.

“Based on preliminary data, pacritinib may be disease modifying and warrants combination studies with other potentially disease-modifying agents in MPNs,” Dr. Mesa said.

RELATED: Primary Myelofibrosis Survival Improving Except for Poor-Risk Patients

The ongoing PERSIST-2 phase 3 trial is exploring pacritinib for the treatment of patients who have thrombocytopenia associated with their disease or its treatment.

Approximately 20,000 people are affected by myelofibrosis in the United States. With the exception of allogeneic hematopoietic stem cell transplant, an infeasible option for many patients, there is no cure. The only FDA approved treatment is the JAK inhibitor, ruxolitinib. Several other agents targeting JAK proteins are in development.

This study received funding from CTI BioPharma Corp.


  1. 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). J Clin Oncol. 2015;33:(suppl; abstr LBA7006).