Dr. Kuykendall on Toxicity Profiles of Ruxolitinib and Fedratinib in Myelofibrosis

Andrew T. Kuykendall, MD, assistant member, Department of Malignant Hematology, Moffitt Cancer Center, discusses the toxicity profiles of ruxolitinib (Jakafi) and fedratinib (Inrebic) in myelofibrosis.

Both agents are JAK inhibitors. However, ruxolitinib targets JAK1/2, whereas fedratinib inhibits JAK2 and FLT3, in addition to some other targets, says Kuykendall.

Fedratinib is associated with increased gastrointestinal toxicities including nausea, vomiting, and diarrhea compared with ruxolitinib, says Kuykendall. These adverse events may be mitigated with prophylactic antiemetics or by eating high-fat meals.

Notably, fedratinib comes with a black box warning for encephalopathy. The randomized phase III JAKARTA trial reported 8 cases of encephalopathy, some of which were suspected to be Wernicke’s encephalopathy, says Kuykendall.

The encephalopathy was potentially due to thiamine deficiency. As such, patients receiving fedratinib should have their thiamine levels checked regularly. Additionally, patients should have thiamine repletion before starting fedratinib, concludes Kuykendall.