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What Setting Should Clinicians Use Fedratinib to Treat Patients With Myelofibrosis?

A roundtable discussion, moderated by Ruben Mesa, MD, of the Atrium Health Wake Forest Baptist Comprehensive Cancer Center, focused on the latest updates in myeloproliferative neoplasms. Dr. Mesa was joined by Naveen Pemmaraju, MD, of the University of Texas MD Anderson Cancer Center; Sanam Loghavi, MD, of the MD Anderson Cancer Center; and Olatoyosi Odenike, MD, of the University of Chicago Medicine. In the fifth segment of the roundtable series, the panel discusses fedratinib treatment for myelofibrosis. — Dr. Mesa: What factors drive clinical decisions regarding treating patients with fedratinib? Do you use it in the frontline or second-line setting? Dr. Odenike: I've used fedratinib in the frontline only in the setting of a clinical trial. Generally, I have reserved fedratinib for the second-line based on clinical trial data that show that the drug is effective in the second-line post ruxolitinib failure. Like with ruxolitinib, now that we have these armamentaria of other Janus kinase (JAK) inhibitors, I favor using fedratinib in folks who have a large spleen, but hematopoiesis is still reasonably well-preserved. I do think that fedratinib has significant potential to improve splenomegaly, even in the second-line. The reason I don’t reach for it in the first-line is because of tolerability. There are many reports of patients going on and off fedratinib so rapidly, and that all hearkens back to tolerability. Dr. Mesa: I have used fedratinib in the frontline, but specifically in patients who are JAK inhibitor naive and had multiple skin cancer issues or difficulties with herpes zoster. Dr. Pemmaraju: The major issue has been gastrointestinal (GI) toxicity. When I am prescribing fedratinib, I'm generally prescribing three other drugs. I'm checking thiamin as the black box warning indication. Nausea and diarrhea are a serious concern for some patients. Therefore, I’m giving antiemetics, antidiarrhea, and thiamin at baseline. This is a lot. Now, you're following the patients over time. If someone develops an encephalopathy event, this is a serious event in the clinic. I'm doing [magnetic resonance imaging] of the brain, neurology consultation, etc. But GI is a serious issue. When I'm counseling my patients, and they have a major GI comorbidity, we may stay away from this drug for that indication.