Dr Hunter on the Current Treatment Landscape of JAK Inhibitor Treatment in Myelofibrosis

Anthony M Hunter, MD, assistant professor, Department of Hematology and Medical Oncology Emory University School of Medicine, medical director, Immediate Care Center, Winship Cancer Institute of Emory University, discusses the current treatment landscape with JAK inhibitors in myelofibrosis.

At the 2023 SOHO Annual Meeting, Hunter presented factors to consider when selecting a JAK inhibitor when treating a patient with myelofibrosis. Hunter explains that not all patients require a JAK inhibitor. For those who do require a JAK inhibitor, Hunter emphasizes that the optimal JAK inhibitor use remains ruxolitinib (Jakafi) in the frontline proliferative setting, pacritinib (Vonjo) in the frontline cytopenic setting, and either fedratinib (Inrebic), momelotinib, pacritinib, or other novel agents following ruxolitnib progression.

Patients could become intolerant to a JAK inhibitor or become resistant or refractory to a treatment, Hunter says, adding that, historically, these patients have poor overall survival outcomes. Although the JAK/STAT pathway is critical in the pathogenesis of myelofibrosis, the overall mechanisms for JAK inhibitors in the treatment of these patients are not fully understood yet, he explains. However, there are many other viable signaling pathways to target for this patient population, including the PI3K or the RAS/MAPK pathway, which are activated in myelofibrosis, Hunter emphasizes.

Historically, following progression on or after ruxolitinib, patients typically have a very short overall survival prognosis, specifically with the previous lack of beneficial treatment options within this landscape, Hunter continues. With the advent of multiple emerging JAK inhibitors that have been approved or are under development, the future remains bright, with many of these new agents now being investigated in the second-line, post-ruxolitinib setting. With more options available, there is now a chance to treat some patients with another JAK inhibitor. Ongoing clinical trials are also an option for patients following ruxolitinib, and these studies remain important for this patient population, he concludes.