Dr Jain on Treatment Decision-Making With JAK Inhibitors in Myelofibrosis

“Out of the 4 JAK inhibitors we have FDA-approved, the harder part is choosing a JAK inhibitor for [a patient] who has cytopenias. Even before that, the question is: does everyone with myelofibrosis need a JAK inhibitor? Not necessarily.”

Akriti G. Jain, MD, a hematologist and medical oncologist at the Cleveland Clinic, detailed the approach to JAK inhibitor selection for the treatment of patients with myelofibrosis in clinical practice.

Based on the 4 JAK inhibitors that have been FDA-approved for the treatment of patients with myelofibrosis, a challenge when selecting treatment is when a patient presents with cytopenias, Jain began. She emphasized that a significant question also arises: do all patients with myelofibrosis require a JAK inhibitor? If a patient has lower-risk disease per risk stratification using the Molecular International Prognostic Scoring System 2.0 and they do not have an enlarged spleen or heavy symptom burden, they may not require a JAK inhibitor and could undergo observation, she explained.

If a patient has intermediate- to high-risk disease with an enlarged spleen or the presence of symptoms, there are factors to consider when selecting a JAK inhibitor, according to Jain. If the patient’s counts look good, then selecting ruxolitinib (Jakafi) first would be the option, based on its efficacy regarding both spleen and symptom responses. If the patient has anemia, especially if they are transfusion dependent, then ruxolitinib may not be the ideal initial option, as ruxolitinib could cause anemia during therapy, she asserted. Of note, reducing the dose of ruxolitinib may not be ideal, namely because receiving less of the dose means less of a benefit, she explained. In cases where patients present with anemia, selecting momelotinib (Ojaara) could be a feasible option, notably because of its ACVR1 inhibition to provide anemia benefit.

Nevertheless, in the phase 3 SIMPLIFY-1 (NCT01969838), which compared momelotinib with ruxolitinib as frontline therapy, data revealed that momelotinib was noninferior for spleen response of spleen volume reduction by 25% or more at week 24, Jain continued. Still, ruxolitinib demonstrated better symptom control compared with momelotinib. Treatment selection depends on every patient; therefore, if their symptoms, spleen volume, or anemia are major burdens, respectively, treatment could differ, she concluded.