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Clinical Validation of KIT Inhibition in Advanced Systemic Mastocytosis.
Curr Hematol Malig Rep 2018; 13(5):407-416CH

Abstract

PURPOSE OF REVIEW

We discuss recent developments in the treatment of advanced systemic mastocytosis (advSM) with inhibitors of the KIT receptor tyrosine kinase.

RECENT FINDINGS

advSM is a heterogeneous group of neoplasms of poor prognosis characterized by the accumulation of neoplastic mast cells. The canonical KIT D816V mutation is present in approximately 90% of SM patients, and its detection is critical for both diagnosis and therapeutic decision-making. The multikinase/KIT inhibitor midostaurin was recently approved for advSM. This agent can reverse SM-related organ damage and disease symptoms, and decrease the bone marrow mast cell burden and splenomegaly. However, complete remissions are rare and durability of responses is variable. Potent and selective KIT D816V inhibitors including avapritinib (BLU-285) and DCC-2618 have entered clinical trials, and rational combination strategies are under development. The clinical efficacy of KIT inhibitors validate KIT as a key oncogenic driver in mast cell neoplasms. An improved understanding of the genetic heterogeneity beyond KIT will help inform the dynamics of response and relapse.

Authors+Show Affiliations

Division of Hematology, Stanford Cancer Institute / Stanford University School of Medicine, 875 Blake Wilbur Drive, Room 2324, Stanford, CA, 94305-5821, USA.Division of Hematology, Stanford Cancer Institute / Stanford University School of Medicine, 875 Blake Wilbur Drive, Room 2324, Stanford, CA, 94305-5821, USA. jason.gotlib@stanford.edu.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

30155614

Citation

Baird, John H., and Jason Gotlib. "Clinical Validation of KIT Inhibition in Advanced Systemic Mastocytosis." Current Hematologic Malignancy Reports, vol. 13, no. 5, 2018, pp. 407-416.
Baird JH, Gotlib J. Clinical Validation of KIT Inhibition in Advanced Systemic Mastocytosis. Curr Hematol Malig Rep. 2018;13(5):407-416.
Baird, J. H., & Gotlib, J. (2018). Clinical Validation of KIT Inhibition in Advanced Systemic Mastocytosis. Current Hematologic Malignancy Reports, 13(5), pp. 407-416. doi:10.1007/s11899-018-0469-3.
Baird JH, Gotlib J. Clinical Validation of KIT Inhibition in Advanced Systemic Mastocytosis. Curr Hematol Malig Rep. 2018;13(5):407-416. PubMed PMID: 30155614.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical Validation of KIT Inhibition in Advanced Systemic Mastocytosis. AU - Baird,John H, AU - Gotlib,Jason, PY - 2018/8/30/pubmed PY - 2019/4/19/medline PY - 2018/8/30/entrez KW - Avapritinib KW - Imatinib KW - KIT D816V KW - Midostaurin KW - Systemic mastocytosis SP - 407 EP - 416 JF - Current hematologic malignancy reports JO - Curr Hematol Malig Rep VL - 13 IS - 5 N2 - PURPOSE OF REVIEW: We discuss recent developments in the treatment of advanced systemic mastocytosis (advSM) with inhibitors of the KIT receptor tyrosine kinase. RECENT FINDINGS: advSM is a heterogeneous group of neoplasms of poor prognosis characterized by the accumulation of neoplastic mast cells. The canonical KIT D816V mutation is present in approximately 90% of SM patients, and its detection is critical for both diagnosis and therapeutic decision-making. The multikinase/KIT inhibitor midostaurin was recently approved for advSM. This agent can reverse SM-related organ damage and disease symptoms, and decrease the bone marrow mast cell burden and splenomegaly. However, complete remissions are rare and durability of responses is variable. Potent and selective KIT D816V inhibitors including avapritinib (BLU-285) and DCC-2618 have entered clinical trials, and rational combination strategies are under development. The clinical efficacy of KIT inhibitors validate KIT as a key oncogenic driver in mast cell neoplasms. An improved understanding of the genetic heterogeneity beyond KIT will help inform the dynamics of response and relapse. SN - 1558-822X UR - https://www.unboundmedicine.com/medline/citation/30155614/Clinical_Validation_of_KIT_Inhibition_in_Advanced_Systemic_Mastocytosis_ L2 - https://dx.doi.org/10.1007/s11899-018-0469-3 DB - PRIME DP - Unbound Medicine ER -