Mechanism of Action of Pacritinib

EP: 1.Case Presentation: A 76-Year-Old Woman with Myelofibrosis

EP: 2.Clinical Phenotypes in Patients with Myelofibrosis

EP: 3.Considerations in Choosing a Treatment for Myelofibrosis

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EP: 4.Mechanism of Action of Pacritinib

EP: 5.Review of the PERSIST-1 and PERSIST-2 Trials

EP: 6.The Future of Myelofibrosis Treatment

Case: A 76-Year-Old Woman with Myelofibrosis

Initial presentation

• SM is a 76 y/o woman who visits her primary care physician for her annual checkup. She reports having fatigue, occasional night sweats and abdominal discomfort under left rib for the past 2 months. She also mentioned that she feels pain in her bones, but she just attributes that to her “old age.”
  • SM spends most of her days gardening followed by baking, her 2 favorite activities. Lately, she feels tired after just spending 1 hour gardening and has no energy to bake afterwards.
  • Since her last examination a year ago, SM has lost close to 12 lbs. She says she has not been dieting and has not noticed a change in her eating habits.
  • PMH:
    • Hypertension (controlled)
    • Glaucoma
    • Asthma (controlled with inhalers)
  • SMH: (-) nonsmoker; has an occasional drink during book club with her girlfriend
  • FH: she lives alone but her daughter and sister live close by; no family history of cancer
  • PE: abdominal exam reveals spleen palpable 4cm below left coastal margin visible bruising
    

Clinical workup

• Current Labs: (baseline labs were within normal limits at her last examination one year ago)
  • Platelet count: 44 x 109/L
  • Hgb: 8g/dL
  • WBC count: 27 x 109/L
• Bone Marrow Biopsy
  • Shows a hypercellular bone marrow, increase in atypical appearing megakaryocytes and MF-2 fibrosis, no increase in blasts by CD34+ IHC, aspirate without spicules
• Molecular testing
  • JAK-V617F mutation: positive at 44%, NGS panel only identified TET2 mutation at a VAF of 17%
    

Treatment

• SM complaining of increasing fatigue and abdominal pain and on PE, shows splenomegaly
• Treatment started with pacritinib 200mg BID