Dr. Saint Fleur-Lominy on Differences Between Ruxolitinib and Fedratinib in MPNs

Shella Saint Fleur-Lominy, MD, PhD, an assistant professor at NYU Langone Health’s Perlmutter Cancer Center, discusses the differences between ruxolitinib (Jakafi) and fedratinib (Inrebic) in myeloproliferative neoplasms (MPNs).

Compared with ruxolitinib which targets JAK1/2, fedratinib is more selective for JAK2 and targets other kinases, such as FLT3, says Saint Fleur-Lominy. However, the role of FLT3 inhibition in MPNs is not well defined.

According to findings from the phase III JAKARTA which showed potential cases of Wernicke’s encephalopathy, the FDA placed a clinical hold on fedratinib, explains Saint Fleur-Lominy. The FDA lifted the clinical hold in August 2017 and fedratinib was subsequently approved in August 2019 for the treatment of patients with intermediate-2 or high-risk primary or secondary myelofibrosis.

Fedratinib is an alternative therapy for patients who cannot tolerate ruxolitinib due to significant cytopenia, says Saint Fleur-Lominy. Though cytopenia can occur with fedratinib, the risk of thrombocytopenia is decreased compared with ruxolitinib.

The risk of encephalopathy may deter some physicians from utilizing fedratinib in the clinic. However, measuring thiamine levels and monitoring patients carefully can lead to reduced risk, concludes Saint Fleur-Lominy.