Current Hematologic Malignancy Reports

, Volume 13, Issue 5, pp 407–416 | Cite as

Clinical Validation of KIT Inhibition in Advanced Systemic Mastocytosis

  • John H. Baird
  • Jason GotlibEmail author
Myeloproliferative Neoplasms (B Stein, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Myeloproliferative Neoplasms


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.


Systemic mastocytosis KIT D816V Midostaurin Avapritinib Imatinib 


Compliance with Ethical Standards

Conflict of Interest

Dr. Gotlib has, or will be serving, as Study Steering Committee Chairman or Co-Chairman of trials involving midostaurin, avapritinib, and DCC-2618 in advanced systemic mastocytosis (AdvSM). His institution received funding for conduct of these clinical trials, as well as brentuximab vedotin, for which he was principal investigator. Dr. Gotlib has also served on advisory boards, received honoraria, and reimbursement for travel expenses from Novartis, Blueprint Medicines, and Deciphera, Inc.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


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Authors and Affiliations

  1. 1.Division of HematologyStanford Cancer Institute / Stanford University School of MedicineStanfordUSA

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