Patient-Tailored JAK Inhibitor Selection: Evaluating Ruxolitinib, Fedratinib, Pacritinib, and Momelotinib in Intermediate-Risk Disease
Panelists discuss how to select among the four available JAK inhibitors (Ruxolitinib, Fedratinib, Pacritinib, and Momelotinib) based on patient-specific factors such as anemia, thrombocytopenia, and symptom burden.
In this segment, the experts discuss the selection criteria among four available JAK inhibitors—ruxolitinib, fedratinib, pacritinib, and momelotinib—for myelofibrosis treatment. Dr. Rampal notes that both ruxolitinib and fedratinib demonstrate effectiveness in reducing spleen size and improving symptoms based on the COMFORT and JAKARTA trials, respectively. However, both medications cause thrombocytopenia and anemia as expected on-target effects.
For the case patient with hemoglobin of 9.7, Dr. Rampal emphasizes that anemia management depends on the patient’s context, including comorbidities and ability to tolerate potential hemoglobin drops. Momelotinib offers an advantage with less anemia, though the SIMPLIFY-1 trial showed similar spleen response, but inferior symptom response compared to ruxolitinib. The choice between these medications should consider the patient’s specific symptom burden and ability to tolerate anemia.
Dr. Vachhani agrees that having multiple JAK inhibitor options benefits patients, allowing physicians to select the most appropriate agent based on individual characteristics. He mentions that supportive care medications can be used alongside JAK inhibitors, as recommended by NCCN guidelines. Dr. Rampal discusses using erythropoietin-stimulating agents when endogenous erythropoietin levels are under 250, luspatercept (particularly in combination with ruxolitinib based on phase 2 data), and older options like thalidomide and danazol. He emphasizes that supportive treatments should target symptomatic anemia rather than just laboratory values.
