Dr Amanam on Criteria for Selecting a JAK Inhibitor in Myelofibrosis

Idoroenyi Amanam, MD, assistant professor, Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, discusses the criteria for selecting JAK inhibitors in the treatment of patients with myelofibrosis.

Ruxolitinib (Jakafi) was the first JAK inhibitor approved for the treatment of myelofibrosis by the FDA in 2011. Amanam notes that this approval was initially based on the agent’s demonstrated benefits in reducing splenomegaly and improving symptom burden, two critical factors that influence treatment outcomes in myelofibrosis. Since then, 3 additional JAK inhibitors have received FDA approval for the treatment of select patients with myelofibrosis: fedratinib (Inrebic) in 2019, pacritinib (Vonjo) in 2022, and momelotinib (Ojjaara) in 2023.

Amanam emphasizes that the ideal candidates for JAK inhibitors are patients experiencing significant symptom burden and splenomegaly. Patients presenting with myelofibrosis, particularly those with moderate to severe spleen enlargement and a high burden of disease-related symptoms, are likely to derive the most benefit from JAK inhibition, he continues.

Conversely, patients who are not experiencing splenomegaly or any symptom burden may have limited therapeutic gain from JAK inhibitors, and the use of these agents in these patients may expose them to unnecessary risks of adverse effects (AEs), he says. The most commonly reported AEs from JAK inhibitor treatment are cytopenias, such as anemia, thrombocytopenia, and leukopenia, Amanam notes.

To avoid these potential toxicities, Amanam stresses the importance of thorough patient evaluation and symptom assessment when considering JAK inhibitors, as the absence of these key criteria can reduce the overall efficacy of treatment and increase the potential for unnecessary AEs.

In clinical practice, Amanam explains the importance of personalized treatment strategies based on individual patient characteristics and risk profiles, prioritizing those who meet the established clinical benchmarks for symptom relief and splenic volume reduction.

Although JAK inhibitors can offer significant symptomatic relief for appropriately selected patients, they are not universally beneficial for all patients with myelofibrosis and should be used judiciously to optimize clinical outcomes, he concludes.