Dr. Mascarenhas on the Benefit of Fedratinib 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 benefit of fedratinib (Inrebic) for patients with myelofibrosis.

Fedratinib is a potent and selective JAK2 inhibitor that spares JAK1, which differentiates the agent from ruxolitinib (Jakafi), Mascarenhas begins. However, fedratinib is similar in many ways to pacritinib (Vonjo), as both are JAK2-specific inhibitors that inhibit FLT3, Mascarenhas adds. Moreover, fedratinib has shown that to be very active in 2 previous trials, including the phase 3 JAKARTA trial (NCT01437787) and the phase 2 JAKARTA2 trial (NCT01523171), Mascarenhas emphasizes. In these trials, fedratinib was active in achieving spleen responses and symptom burden improvement, Mascarenhas notes.

In the second line, particularly where there was an unmet need for patients with myelofibrosis, there is a commercially available option of fedratinib to salvage spleen and symptom burden in patients who either did not achieve spleen or symptom improvement with up-front ruxolitinib or lost that response, Mascarenhas continues. Therefore, fedratinib is a viable option to address spleen and symptom burden after ruxolitinib, Mascarenhas notes.

Since fedratinib is myelosuppressive, it can lead to cytopenias. Fedratinib is dosed at 400 mg once daily, and there is a warning of Wernicke's encephalopathy, Mascarenhas says. Given this warning, clinicians should check patients for levels of vitamin B1 and thymine levels before dosing with fedratinib, then every 3 months, Mascarenhas notes, adding that patients can also be supplemented with vitamin B1.

Fedratinib is a viable option for patients in the community that need a commercially available drug to address spleen and symptom burden, Mascarenhas concludes.