The Evolving Landscape of Myelofibrosis: Current Understanding and Clinical Patterns
Panelists discuss how evolving insights into myelofibrosis—driven by molecular profiling, risk-adaptive therapy, and emerging treatments—are reshaping clinical practice toward more personalized care, with increasing focus on managing cytopenias, treatment resistance, and long-term disease modification.
Summary for Physicians:
Current Myelofibrosis Landscape and Evolving Understanding:
The myelofibrosis (MF) treatment landscape has significantly evolved over recent years, shifting from a primary focus on symptom management and splenomegaly reduction toward a more nuanced understanding of disease biology, prognosis, and individualized therapy.
Key Developments:
- Molecular Profiling: There is now greater emphasis on driver mutations (eg, JAK2, CALR, MPL) and high-risk mutations (eg, ASXL1, SRSF2, EZH2), which have improved risk stratification and guide treatment decisions.
- Risk-Adaptive Therapy: Treatment is increasingly based on disease risk, symptom burden, and mutation profile, with tools like DIPSS, MIPSS70, and GIPSS being used more routinely.
- JAK Inhibitors: The approval and widespread use of Janus kinase (JAK) inhibitors, particularly ruxolitinib and fedratinib, have transformed symptom control and splenomegaly management. Newer agents like momelotinib and pacritinib are also expanding options, especially for patients with anemia or thrombocytopenia.
- Emerging Therapies: Ongoing research into combination regimens, non-JAK targeted therapies, and disease-modifying agents is reshaping expectations beyond symptom control toward modifying disease progression.
Current Patterns in Disease Presentation and Progression:
In clinical practice, several patterns are now more commonly recognized:
- Heterogeneous Presentations: Patients may present with asymptomatic cytopenias, isolated constitutional symptoms, or significant splenomegaly and bone marrow fibrosis. Presentation can vary widely depending on mutation profile and disease phase.
- Progressive Cytopenias: Anemia is a frequent and often worsening issue, even in patients on JAK inhibitors. Some patients may progress toward transfusion dependence, impacting both treatment options and prognosis.
- Risk of Leukemic Transformation: A subset of patients progresses to acute myeloid leukemia, often associated with high-risk mutations or prolonged disease course, underscoring the importance of molecular monitoring.
- Treatment Resistance or Intolerance: A growing clinical challenge is resistance to JAK inhibitors or treatment intolerance due to cytopenias, highlighting the need for alternative options and combination strategies.
Overall, the approach to managing myelofibrosis has become more personalized, with increased use of molecular and clinical risk stratification, attention to cytopenias, and a shift toward identifying patients who may benefit from curative approaches like allogeneic stem cell transplant or participation in clinical trials for investigational agents.
