Consistency of spleen and symptom reduction regardless of cytopenia in patients with myelofibrosis treated with pacritinib

Abstract

Cytopenias are common in patients with myelofibrosis (MF). The efficacy of the JAK2/IRAK1/ACVR1 inhibitor pacritinib was analyzed by baseline platelet and hemoglobin levels using data from 2 Phase 3 studies in patients with MF. Pacritinib demonstrated spleen volume reduction and symptom responses across hemoglobin and platelet subgroups, indicating that pacritinib may provide benefit regardless of the presence of severe cytope- nias. Background: Pacritinib is a JAK2/IRAK1/ACVR1 inhibitor that is approved in the United States for the treatment of patients with myelofibrosis who have a platelet count < 50 ×109/L. Phase 3 clinical studies of pacritinib included patients across a wide range of baseline platelet and hemoglobin levels. Patients and Methods: In order to assess the impact of baseline blood counts on pacritinib efficacy, an analysis of efficacy outcomes by baseline platelet and hemoglobin levels was performed using data pooled from 2 Phase 3 studies of pacritinib in patients with MF (PERSIST-1 and PERSIST-2). Results: Of 276 patients evaluable for spleen response, spleen volume reduction occurred consistently across platelet subgroups ( < 100 ×109/L or ≥100 ×109/L) and hemoglobin subgroups ( < 8 g/dL, ≥8 to < 10 g/dL, or > 10 g/dL), with no diminution in treatment effect in patients with severe thrombocytopenia or anemia. Among 159 patients evaluable for symptoms response, improvement in total symptom score (TTS) was similar across platelet subgroups. A ≥50% improvement of TSS occurred more frequently in patients with baseline hemoglobin < 8 g/dL compared with those with baseline hemoglobin ≥8 to < 10 g/dL or > 10 g/dL. Patients with baseline hemoglobin < 8 g/dL also experienced improved hemoglobin sustained over 24 weeks, whereas subgroups with less severe anemia had stable hemoglobin levels over time. Symptom improvement as assessed using the Patient Global Impression of Change instrument was generally consistent across platelet and hemoglobin subgroups. Conclusion: Pacritinib demonstrates consistent efficacy in patients with MF regardless of baseline platelet and hemoglobin counts.