A patient with systemic mastocytosis has markedly elevated baseline tryptase. Avapritinib (Blueprint Medicine) is the treatment of choice. Its mechanism involves:
- A H1 and H2 receptor dual blockade preventing mast cell mediator effects
- B Selective inhibition of KIT D816V mutant kinase, the activating mutation driving mast cell proliferation ✓
- C Anti-IgE monoclonal antibody (omalizumab) preventing mast cell degranulation
- D Corticosteroid-mediated inhibition of mast cell synthesis
Explanation
Over 90% of systemic mastocytosis cases harbor the KIT D816V activating point mutation in the tyrosine kinase domain of the KIT receptor (CD117), causing constitutive signaling and uncontrolled mast cell proliferation. Avapritinib is a potent, highly selective type I kinase inhibitor that directly inhibits the KIT D816V mutant with far greater potency than imatinib (which cannot accommodate the conformational change of D816V). It is FDA-approved for advanced systemic mastocytosis. Omalizumab (option C) treats allergic asthma and IgE-mediated urticaria, not the clonal mast cell disease.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.