A 58-year-old man is diagnosed with primary myelofibrosis. He has a leukocyte count of 22,000/µL, massive splenomegaly (18 cm), symptomatic anemia (Hb 8.5 g/dL), and DIPSS-Plus score of intermediate-2. JAK2 V617F mutation is positive. Which agent targets the JAK-STAT pathway and is the standard of care for symptomatic disease in this condition?
- A Hydroxyurea
- B Pegylated interferon-alfa
- C Ruxolitinib ✓
- D Danazol
Explanation
Ruxolitinib is a JAK1/JAK2 inhibitor approved for intermediate and high-risk myelofibrosis. JAK2 V617F mutation leads to constitutive JAK-STAT pathway activation; ruxolitinib inhibits this, reducing splenomegaly, improving constitutional symptoms, and modestly improving survival. The COMFORT-I and COMFORT-II trials demonstrated significant reduction in spleen volume and symptom burden compared to placebo/best available therapy. Hydroxyurea reduces cell counts but does not significantly reduce splenomegaly or improve survival. Pegylated IFN is more useful in early MF and polycythemia vera. Allogenic SCT remains the only potentially curative option for eligible patients.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.