Dr Mascarenhas on First-line Treatment Decisions 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 first-line treatment decisions for patients with myelofibrosis.

Although recent advancements have been made in the myelofibrosis treatment landscape, treatment in the frontline setting has remained largely unchanged over the past decade, Mascarenhas begins. Ruxolitinib (Jakafi) remains the treatment of choice for patients with platelet counts above 50 × 10⁹/L; however, when treating patients with platelet counts below 50 × 10⁹/L , pacritinib (Vonjo) should be used, Mascarenhas says. In February 2022, the FDA granted 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.

Although pacritinib is indicated for patients below the 50 × 10⁹/L platelet threshold, data from the phase 3 PERSIST-2 trial (NCT02055781) showed that the agent has efficacy in patients with platelets less than 100 × 10⁹/L, Mascarenhas continues. However, patients with platelet counts above 100 × 10⁹/L remain great candidates for treatment with ruxolitinib, he adds.

Additionally, fedratinib (Inrebic) could be considered as another option in the first-line setting for patients who have significant splenomegaly, Mascarenhas continues, noting that this agent could effectively reduce spleen size. He adds that fedratinib is typically used in the second-line setting.

Fedratinib does have a simpler dosing regimen in capsule form, and it is typically with a heavy meal to assist with the absorption to reduce some of the gastrointestinal toxicities. However, it is important to warn patients that they can have a degree of nausea and diarrhea; however, these adverse effects are generally manageable during the first few treatment cycles and rarely lead to discontinuation, Mascarenhas concludes.