Topline Presentation Points 

Driver mutations in myeloproliferative neoplasms (MPN) 

Disease complications in polycythemia vera (PV) and essential thrombocythemia (ET) 

  • Increased risk of Thrombosis with 22%+ at diagnosis and 29%+ at follow-up 
  •  AML and MF increase after 10 years 
  • Fibrotic or blastic transformation 
  • Non-life threatening 
    • Pruritus 
    • Microvascular symptoms 
  • Prognostic assessments in PV/ET 

Current Treatment Algorithms 

  • Essential Thrombocythemia 
  • Polycythemia Vera 
    • Stratified by low risk and high risk.  
      • High risk treatment options  
        • Hydroxyurea (500 mg BID starting dose with 
        • Twice daily aspirin for patients with arterial thrombosis history 
        • Systemic  anticoagulation for patients  with venous thrombosis history 
        • For those intolerant or resistant

          Pegylated IFN-α
          (Age <65 yrs)
          (Age >65 yrs)
  • Myelofibrosis – Based on Risk Stratification According to MIPSS70+ Version 2.0  
    • Curative or with potential to improve survival 
      • Allogeneic hematopoietic cell transplant (allo-HCT)  
    • Palliative 
      • Observation alone (watch-and-wait) 
      • Treatment for anemia, symptomatic splenomegaly, constitutional symptoms and other options 

Emerging options – Epigenetic-based Therapies in Myelofibrosis Therapy 

  • Phase II Azacitidine + Ruxolitinib. Mechanism – Hypomethylating agent  
  • Phase I/IIb IMG-7289 (bomedemstat) . Mechanism – LSD1 inhibitor:  histone demethylase specific for H3K4 
  • Phase II CPI-0610 (BET inhibitor) Mechanism – Bromodomain and Extraterminal Domain Inhibitor (BETi).  
  • Phase I/II  SL-401 (Tagraxofusp). Mechanism – CD123-targeted  therapy  
  • Phase II Navitoclax + Ruxolitinib. Mechanism – Binds BCL-X, BCL-2, BCL-W causing apoptosis  
  • Phase II Metformin. Mechanism – Biguanide inhibits multiple oncogenic pathway