Prognostic Stratification on Myelofibrosis: From Models to Clinical Application

EP: 1.The Evolving Landscape of Myelofibrosis: Current Understanding and Clinical Patterns

EP: 2.Diagnostic Challenges in Myelofibrosis: Distinguishing Prefibrotic Disease

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EP: 3.Prognostic Stratification on Myelofibrosis: From Models to Clinical Application

EP: 4.Clinical Decision-Making Framework for Initiating Myelofibrosis Therapy

EP: 5.Early Intervention in Myelofibrosis: Interpreting Survival Evidence

EP: 6.Splenomegaly Management in Myelofibrosis: Symptomatic and Asymptomatic Disease

EP: 7.JAK Inhibitor Therapy: Personalized Selection and Optimization Strategies

EP: 8.Navigating Cytopenia Challenges: Strategic Management Approaches in Myelofibrosis

EP: 9.Novel Therapeutic Pathways in Myelofibrosis: Beyond JAK Inhibition

EP: 10.Defining Treatment Success: End points in Myelofibrosis Clinical Development

Summary for Physicians:

Risk Stratification and Treatment Decision-Making in Myelofibrosis:

Effective management of myelofibrosis (MF) relies heavily on accurate risk stratification, which informs both the urgency and intensity of treatment. The approach to risk assessment integrates clinical features, laboratory data, and increasingly, molecular information, allowing for a more personalized treatment strategy.

Prognostic Tools in Practice:

Several validated scoring systems are commonly used:

• DIPSS/DIPSS-Plus (Dynamic International Prognostic Scoring System):
• Based on age, hemoglobin, leukocyte count, circulating blasts, and symptoms.
• DIPSS-Plus adds platelet count, transfusion dependence, and cytogenetics.
• Useful for ongoing risk assessment throughout disease progression.
• MIPSS70/MIPSS70+ (Mutation-Enhanced Prognostic Scoring System):
• Incorporates clinical features and high-risk mutations (eg, ASXL1, SRSF2, EZH2).
• Designed specifically for patients under the age of 70, especially those being considered for transplant.
• GIPSS (Genetically Inspired Prognostic Scoring System):
• Based solely on genetic and cytogenetic information, without clinical variables.
• Reflects the growing emphasis on molecular profiling in prognosis.

Each tool offers different advantages depending on the patient's age, comorbidities, and whether they are transplant candidates.

Translating Risk Into Treatment Decisions

• Low-Risk Patients:
• Often managed with observation or symptom-directed therapy, especially in the absence of cytopenias or splenomegaly.
• JAK inhibitors may be considered if symptoms are present but not required immediately in asymptomatic cases.
• Intermediate- and High-Risk Patients:
• These patients are typically considered for disease-modifying strategies, including JAK inhibitor therapy and evaluation for allogeneic stem cell transplantation (particularly for transplant-eligible individuals under the age of 70 with high-risk features).
• Symptom Burden and Cytopenias:
• Even within the same risk category, the presence of significant symptoms (eg, constitutional symptoms, splenomegaly) or anemia/thrombocytopenia can drive treatment decisions.
• JAK inhibitors such as ruxolitinib, fedratinib, momelotinib, or pacritinib are selected based on the patient’s blood counts and symptom profile.
• Transplant Consideration:
• Patients with high-risk mutations or aggressive disease features may be referred for transplant evaluation earlier, even in the absence of overt clinical progression.

In summary, the choice of prognostic model is guided by patient-specific factors, and risk assessment plays a central role in determining the timing and intensity of therapy—from watchful waiting in low-risk disease to early referral for transplant in high-risk patients.