Myelofibrosis Management: Clinical Approaches and Treatment Algorithms With Case-Based Application

Summary of Myelofibrosis Treatment Approach and Case Discussion

Treatment Algorithm Overview

• Lower-risk myelofibrosis:
  • Observation is appropriate for asymptomatic patients
  • For symptomatic or spleen-related issues: Janus kinase (JAK) inhibitors (including pacritinib for platelets <50,000/μL), or peginterferon alfa-2a
• Higher-risk myelofibrosis with platelets >50,000/μL:
  • Four JAK inhibitor options per NCCN guidelines:
    • Ruxolitinib and fedratinib: Category 1 recommendation
    • Momelotinib: Category 2A recommendation
    • Pacritinib: Category 2B recommendation
  • Continual monitoring for response or progression
  • Switch to alternate JAK inhibitor if no/lost response
  • Consider different therapy approach for disease progression

Case Presentation: Intermediate-Risk Myelofibrosis

Patient Profile:

• 68-year-old woman with mild fatigue
• Spleen 7 cm below left costal margin
• No known comorbidities
• Labs: white blood cells 23,000/μL, hemoglobin (Hb) 9.7 g/dL, platelets 450,000/μL, <1% blasts
• JAK2 V617F mutation positive, normal karyotype
• Risk assessment: DIPSS intermediate-1 risk, MIPSS70+ version 2.0 intermediate risk
• Patient not interested in transplant

Treatment Considerations

JAK Inhibitor Selection:

• JAK inhibitor recommended for significant symptomatic splenomegaly
• Adequate platelet count (450,000/μL) allows flexibility in JAK inhibitor choice
• For Hb 9.7 g/dL: momelotinib or pacritinib may offer anemia benefits
• Ruxolitinib remains reasonable despite potential anemia concerns

Treatment Goals:

1. Spleen-related:
   1. Reduce pain and discomfort
   2. Improve ability to eat full meals
   3. Maintain patient weight
2. Anemia management:
   1. Maintain Hb >9.0 g/dL
   2. Avoid transfusion dependence
3. Symptom improvement:
   1. Address constitutional symptoms
   2. Improve quality of life
4. Long-term objectives:
   1. Prevent worsening cytopenias
   2. Potentially improve survival outcomes

The panel emphasized the importance of establishing clear treatment goals, monitoring response, and considering JAK inhibitor characteristics when selecting therapy for intermediate-risk myelofibrosis patients.