TY - JOUR
T1 - Avapritinib for Systemic Mastocytosis
AU - Bose, Prithviraj
AU - Verstovsek, Srdan
N1 - Publisher Copyright:
© 2021 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2021
Y1 - 2021
N2 - Introduction: Systemic mastocytosis (SM) is a rare myeloid neoplasm driven in ≈95% of cases by activating KIT mutations, usually D816V. SM can be indolent (ISM), smoldering (SSM) and advanced (AdvSM), the latter characterized by organ damage resulting from infiltrating neoplastic mast cells. The vast majority of cases are indolent, with near-normal life expectancy, although symptoms can be severe. AdvSM, comprising aggressive SM, SM with an associated hematologic neoplasm and mast cell leukemia, however, carries a poor prognosis. Avapritinib is a highly potent and selective inhibitor of mutant KIT. Areas Covered: We provide an overview of SM, including the current therapeutic landscape, and discuss avapritinib in detail: its chemistry and discovery, pharmacodynamic and pharmacokinetic data, current approval status and safety and efficacy profiles in both advanced and non-advanced SM. Expert Opinion: With a response rate of 75% amongst evaluable patients with AdvSM and marked reductions observed in measures of mast cell and disease burden, avapritinib stands out as a highly effective targeted therapy for this mutant KIT-driven disease. Cognitive impairment may occur, and intracranial hemorrhage has been reported, particularly in association with severe thrombocytopenia. Early results in patients with ISM/SSM are encouraging. Avapritinib is now approved in the US for AdvSM.
AB - Introduction: Systemic mastocytosis (SM) is a rare myeloid neoplasm driven in ≈95% of cases by activating KIT mutations, usually D816V. SM can be indolent (ISM), smoldering (SSM) and advanced (AdvSM), the latter characterized by organ damage resulting from infiltrating neoplastic mast cells. The vast majority of cases are indolent, with near-normal life expectancy, although symptoms can be severe. AdvSM, comprising aggressive SM, SM with an associated hematologic neoplasm and mast cell leukemia, however, carries a poor prognosis. Avapritinib is a highly potent and selective inhibitor of mutant KIT. Areas Covered: We provide an overview of SM, including the current therapeutic landscape, and discuss avapritinib in detail: its chemistry and discovery, pharmacodynamic and pharmacokinetic data, current approval status and safety and efficacy profiles in both advanced and non-advanced SM. Expert Opinion: With a response rate of 75% amongst evaluable patients with AdvSM and marked reductions observed in measures of mast cell and disease burden, avapritinib stands out as a highly effective targeted therapy for this mutant KIT-driven disease. Cognitive impairment may occur, and intracranial hemorrhage has been reported, particularly in association with severe thrombocytopenia. Early results in patients with ISM/SSM are encouraging. Avapritinib is now approved in the US for AdvSM.
KW - Avapritinib
KW - advanced sm
KW - aggressive sm (asm)
KW - c-findings
KW - indolent sm
KW - kit d816v
KW - mast cell leukemia (mcl)
KW - midostaurin
KW - sm with an associated hematologic neoplasm (sm-ahn)
KW - systemic mastocytosis (sm)
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UR - http://www.scopus.com/inward/citedby.url?scp=85112639863&partnerID=8YFLogxK
U2 - 10.1080/17474086.2021.1959315
DO - 10.1080/17474086.2021.1959315
M3 - Article
C2 - 34289787
AN - SCOPUS:85112639863
SN - 1747-4086
VL - 14
SP - 687
EP - 696
JO - Expert review of hematology
JF - Expert review of hematology
IS - 8
ER -