Pacritinib (Vonjo) has emerged as a valuable treatment option for patients with intermediate or high-risk primary or secondary myelofibrosis, particularly those with significant thrombocytopenia. The FDA granted accelerated approval to pacritinib for adult patients with platelet counts below 50 × 109/L, based on positive results from the PERSIST-2 trial. This approval fills a critical gap in the treatment landscape, offering a full-dose therapeutic option for patients who may not tolerate other JAK inhibitors at standard doses.
PERSIST-2 Trial: Efficacy and Safety
The phase 3 PERSIST-2 trial evaluated pacritinib in patients with post-essential thrombocythemia myelofibrosis (PET-MF) or post-polycythemia vera myelofibrosis (PPV-MF) and platelet counts of 100 × 109/L or less. Patients were randomized to receive either 200-mg pacritinib twice daily, 400-mg pacritinib once daily, or best available therapy (BAT), which could include ruxolitinib, observation, or symptom-directed treatment. Efficacy was primarily assessed in patients with platelet counts below 50 × 109/L.
The results showed that 29.0% of patients receiving 200-mg pacritinib twice daily experienced a spleen volume reduction of at least 35%, compared to only 3.1% in the BAT group. Additionally, 26% of patients on pacritinib achieved a total symptom score (TSS) reduction of at least 50%, versus 9% on BAT.
Pacritinib's Unique Role in Cytopenic Myelofibrosis
According to Ruben A. Mesa, MD, director of the Mays Cancer Center at The University of Texas Health San Antonio MD Anderson Cancer Center, pacritinib occupies a unique niche in the treatment of cytopenic myelofibrosis. "[Pacritinib] is an important additional JAK2 inhibitor with a unique lane for patients with marked thrombocytopenia or even the broader cytopenic myelofibrosis," Mesa noted. He emphasized that pacritinib can be administered at full dose in patients with platelet counts below 50 × 109/L, a population where other JAK inhibitors like ruxolitinib and fedratinib often require dose reductions due to the risk of exacerbating thrombocytopenia.
Impact on Transfusion Burden and Anemia
Beyond spleen volume and symptom improvement, pacritinib also demonstrated a positive impact on transfusion burden. Among patients who were not transfusion independent at baseline, pacritinib reduced red blood cell (RBC) transfusion burden at week 24. Furthermore, a subset of patients with hemoglobin levels of at least 10 g/dL at baseline experienced an increase of at least 2 g/dL or achieved RBC transfusion independence for at least 8 weeks.
Safety Profile
Pacritinib's safety profile is considered predictable and manageable. The most common adverse events (AEs) observed in the twice-daily pacritinib arm were diarrhea (48%), thrombocytopenia (34%), nausea (32%), anemia (24%), and peripheral edema (20%).
Future Directions
While pacritinib represents a significant advancement in the treatment of myelofibrosis with thrombocytopenia, ongoing research aims to further refine its use and identify predictive biomarkers. Future studies will focus on monitoring molecular and inflammatory markers to better understand the drug's mechanism of action and optimize treatment sequencing.
