Pacritinib Induced Reduction in Splenomegaly, Myelofibrosis Symptoms

The JAK2 and FLT3 inhibitor pacritinib induced significant and sustained spleen volume reduction (SVR) and symptom reduction in patients with myelofibrosis, even those with significant baseline cytopenias, according to the phase III results of the PERSIST-1 study.

According to study researcher Ruben A. Mesa, MD, of the Mayo Clinic in Scottsdale, Arizona, and colleagues, treatment options for patients with myelofibrosis and severe anemia or thrombocytopenia are limited.

“In this randomized, phase 3 study, treatment with pacritinib resulted in a significantly greater proportion of patients achieving SVR of 35% or more at week 24 compared with best available therapy, regardless of the inclusion of patients with low baseline platelet counts and specifically in the subsets of patients with fewer than 100,000 or 50,000 platelets per μL,” the researchers wrote in Lancet Haematology. “Responses to pacritinib were durable, with the proportion of patients achieving SVR of 35% or more maintained through week 108.”

PERSIST-1 was an international multicenter study that enrolled 327 patients with myelofibrosis between January 2013 and August 2014. Patients had high-risk disease and were not excluded for baseline anemia or thrombocytopenia. They were randomly assigned 2:1 to oral pacritinib 400 mg once daily or best available therapy excluding JAK2 inhibitors. The primary endpoint was SVR of 35% or more from baseline to week 24.

After a median follow-up of 23.2 months, 19% of patients assigned pacritinib achieved the primary endpoint compared with 5% of patients assigned to best available therapy (P = .0003). In the intent-to-treat population of patients enrolled with Total Symptom Score (TSS) 2.0, there was no difference in the numbers of patients who achieved a 50% reduction or greater in TSS from baseline to week 24. However, in the evaluable population, 36% of patients assigned pacritinib compared with 14% of patients assigned best available therapy achieved this secondary endpoint. In addition, the proportion of patients assigned pacritinib with a 50% reduction or greater in TSS increased over time through week 48.

The most common grade 3/4 adverse events through week 24 in the pacritinib group were anemia (17%), thrombocytopenia (12%), and diarrhea (5%). For patients assigned best available therapy, the most common grade 3/4 adverse events were anemia (15%), thrombocytopenia (11%), dyspnea (3%), and hypotension (3%). Deaths due to adverse events occurred in 12% of patients assigned pacritinib and 13% of patients assigned best available therapy.