Pacritinib Offers New Hope in Treatment of Advanced Myelofibrosis


Findings from a phase III randomized clinical trial offer new hope to some patients who have advanced myelofibrosis.

Patients with myelofibrosis often have limited treatment options, but results from a new study published in the Journal of the American Medical Association offer new hope.

In phase III of the global PERSIST-2 clinical trial, pacritinib, an oral JAK2/FLT3 inhibitor, was found to be safe and effective for patients with advanced myelofibrosis (MF) who also have thrombocytopenia. Results of the study were published in the Journal of the American Medical Association.

Trial Design

The PERSIST-2 trial included 311 patients with MF who had platelet counts less than 100,000, an enlarged spleen and systemic symptoms. Many of the patients (48 percent) were either previously treated with ruxolitinib (Jakafi)—an oral JAK inhibitor approved by the Food and Drug Administration (FDA)—or ineligible for treatment with ruxolitinib because of low platelet counts.

“This trial was important as it demonstrated that in a population with very advanced disease as measured by significant thrombocytopenia that limits the ability to effectively receive Jakafi, or have previously failed Jakafi, pacritinib was effective in reducing spleen size and improving symptom burden at the dose of 200 mg twice daily,” John Mascarenhas, MD, associate professor of medicine, hematology and medical oncology at The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai in New York City, said in an interview with Oncology Nursing News.

“Importantly, almost half the patients had received Jakafi previously and half that were randomized to best available therapy received Jakafi. This further highlights the unmet need and lack of effective therapies for this patient population,” he added.

Researchers conducted the study from July 2014 to February 2016, which included 171 men and 140 women, who had a mean age of 63.7 years. Patients were randomly selected to receive 400 mg of pacritinib once daily (75 patients), 200 mg of pacritinib twice daily (74 patients) or best available therapy (72 patients), which included ruxolitinib.

Co-primary end points were rates of patients achieving 35 percent or more spleen volume reduction (SVR) and 50 percent or more reduction in total symptom score (TSS) at week 24.

Pacratinib Found to Be Superior to Best Available Therapies

The researchers determined that the 200 mg twice daily dose was superior to best available therapies in both endpoints. In the twice daily pacritinib arm, SVR was seen in 16 patients compared with two patients who received best available therapy. Reduction in TSS occurred in 24 patients compared with 10 patients, respectively.

“The most significant finding was that at 200 mg twice daily of pacritinib, clinical response was attained in many treated subjects and significant treatment emergent anemia or thrombocytopenia was not seen,” Mascarenhas said. “This offers these patients most in need of treatment, and historically the most vulnerable to disease and therapy-related complications, a therapeutic option either second line after Jakafi or first line in those with baseline limiting cytopenias.”

Adverse Effects

The most common grade 3 or 4 adverse effects were thrombocytopenia and anemia. Discontinuation because of side effects occurred in 15 patients in the pacritinib once daily arm, 10 patients in the twice daily arm and 4 patients in best available therapy arm.


In 2016, the FDA put a full clinical hold on the PERSIST-2 study following concerns from early analysis over increased mortality because of increased risk of bleeding and cardiovascular events.

“Once the full analysis was presented and the survival curves did not show a worse outcome with pacritnib therapy and that the risk of serious bleeding and vascular complications was low, and not clearly different from best available therapy, the hold was lifted in January 2017,” said Mascarenhas.

Further Study

To further investigate pacritinib, the phase 2 PAC203 trial is underway to explore the drug given in lower doses—200 mg twice daily, 100 mg twice daily, and 100 mg once daily. Patients are currently being enrolled.

“This trial will help clarify the relationship between dose and response with drug exposure through pharmacokinetic studies,” Mascarenhas said.

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