Dr Hunter on the Management Ruxolitinib-Associated AEs 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 challenges associated with the management of ruxolitinib (Jakafi)-associated toxicities in patients with myelofibrosis.

Ruxolitinib-based regimens have been a cornerstone treatment for patients with myelofibrosis for over a decade. Prior research has demonstrated the agent's ability to significantly reduce splenomegaly and generally improve symptomatology, Hunter begins. However, one of the major limitations in routine clinical practice is the drug's propensity to cause cytopenias, Hunter says, adding that a considerable drop in both hemoglobin and platelet counts is observed in the majority of patients treated with ruxolitinib. Typically, hemoglobin levels can decrease by approximately 1.5 g within the first 8 to 12 weeks of treatment, after which they may stabilize and improve slightly, he explains. Nonetheless, some degree of persistent drug-related anemia is common, along with a dose-dependent decrease in platelet counts, Hunter notes.

These hematological adverse effects (AEs) can significantly impact treatment decisions, particularly in patients with different phenotypes of myelofibrosis, Hunter continues. For example, patients with a more proliferative phenotype characterized by significant splenomegaly and elevated counts may tolerate ruxolitinib better vs those with a cytopenic phenotype who already have low baseline blood counts, Hunter explains. In the latter group, exacerbating existing cytopenias complicates treatment.

Overall, the need to manage cytopenias carefully while maintaining effective dosing of ruxolitinib poses a challenge for clinicians. In real-world clinical practice, especially in community settings, these cytopenias often necessitate dose reductions and sometimes early cessation of therapy, which can adversely affect patient outcomes and survival, Hunter concludes.