Results of a phase 2 study of pacritinib (SB1518), a JAK2/JAK2(V617F) inhibitor, in patients with myelofibrosis

Abstract

Pacritinib (SB1518) is a Janus kinase 2 (JAK2), JAK2(V617F), and Fms-like tyrosine kinase 3 inhibitor that does not inhibit JAK1. It demonstrated a favorable safety profile with promising efficacy in phase 1 studies in patients with primary and secondary myelofibrosis (MF). This multicenter phase 2 study further characterized the safety and efficacy of pacritinib in the treatment of patients with MF. Eligible patients had clinical splenomegaly poorly controlled with standard therapies or were newly diagnosed with intermediate- or high-risk Lille score. Patients with any degree of cytopenia were eligible. Thirty-five patients were enrolled. At entry, 40% had hemoglobin <10 g/dL and 43% had platelets <100 000× 10(9)/L. Up to week 24, 8 of 26 evaluable patients (31%) achieved a ≥35% decrease in spleen volume determined by magnetic resonance imaging and 14 of 33 (42%) attained a ≥50% reduction in spleen size by physical examination. Median MF symptom improvement was ≥50% for all symptoms except fatigue. Grade 1 or 2 diarrhea (69%) and nausea (49%) were the most common treatment-emergent adverse events. The study drug was discontinued in 9 patients (26%) due to adverse events (4 severe). Pacritinib is an active agent in patients with MF, offering a potential treatment option for patients with preexisting anemia and thrombocytopenia. This trial was registered at www.clinicaltrials.gov as #NCT00745550.

© 2015 by The American Society of Hematology.

Figures

Figure 1

Best spleen response. (A) Best percentage change in spleen volume from baseline up to week 24 by MRI. Depicts the maximum percentage of the change in spleen volume from baseline through week 24 for each patient. Each patient has a baseline measurement and at least 1 postbaseline measurement. Patients at or below the 35% threshold horizontal line are spleen-volume responders. (B) Best percentage change in spleen length from baseline up to week 24 by physical examination. Depicts the maximum percentage of the change in spleen length from baseline through week 24 for each patient. Each patient has a baseline measurement and at least 1 postbaseline measurement. Patients at or below the 50% threshold horizontal line are spleen-length responders.

Figure 2

Median percentage change in symptom score over time. Each panel depicts median percentage change in a symptom score from baseline at each 12-week interval on treatment. The number of patients contributing to the median percentage change is below each bar.