Dr. Mascarenhas on the Role of Pacritinib in Myelofibrosis

John Mascarenhas, MD, professor of medicine, the Icahn School of Medicine, Mount Sinai, director, the Center of Excellence for Blood Cancers and Myeloid Disorders, member, the Tisch Cancer Institute, Mount Sinai, discusses the role of pacritinib (Vonjo) in patients with myelofibrosis.

Pacritinib is JAK1-sparing, JAK2, FLT3, IRAK1, and ACVR1 inhibitor used in the treatment of patients with myelofibrosis in the setting of cytopenias at full dose to obtain spleen and symptom benefit, Mascarenhas says. In February 2022, the FDA granted an accelerated approval to pacritinib for the treatment of adult patients with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 × 109/L.

The approval was based on data from the phase 3 PERSIST-1 (NCT01773187), phase 3 PERSIST-2 (NCT02055781), and phase 2 PAC203 (NCT04884191) trials, a dose-finding study, and the ongoing phase 3 PACIFICA trial (NCT03165734) is serving as a confirmatory trial following the agent’s accelerated approval, Mascarenhas expands.

Although pacritinib is approved for patients with platelets less than 50 × 109/L , PERSIST-2 also produced data in patients with a platelet count of less than 100 x 109/L. Prior to the approval of pacritinib, clinicians did not have a JAK2 inhibitor available for patients with a platelet count below that could be administered at the full dose, Mascarenhas notes. The JAK2 inhibitors fedratinib (Inrebic) and ruxolitinib (Jakafi) have labels patients with platelet counts of 50 × 109/L and greater. Since those two agents are more myelosuppressive, clinicians must attenuate the dose when treating patients with a platelet count below 50 × 109/L, reducing the spleen and symptom benefit generated by fedratinib and ruxolitinib, Mascarenhas says. Twenty 20 mg of pacritinib given twice daily can be delivered to patients with platelet counts at 20 × 109/or less and still produce spleen and symptom benefits with a favorable toxicity profile, Mascarenhas continues.

Studies have not demonstrated an increased risk of cardiovascular events with pacritinib, and data have shown reduced myelosuppression. There may be an increased risk of bleeding with pacritinib, and patients who have a known coagulopathy, have bleeding diathesis, or are receiving anticoagulation should be counseled appropriately, Mascarenhas expands. Although it is important consider the potential benefits and risks for each individual patient, pacritinib does provide an efficacious treatment option for patients with myelofibrosis with low platelet counts, Mascarenhas concludes.