Next Article in Journal
RNA Helicases as Shadow Modulators of Cell Cycle Progression
Next Article in Special Issue
Mastocytosis, MCAS, and Related Disorders—Diagnosis, Classification, and Therapy
Previous Article in Journal
Dual Specificity Kinase DYRK3 Promotes Aggressiveness of Glioblastoma by Altering Mitochondrial Morphology and Function
Previous Article in Special Issue
Epigenetic Changes in Neoplastic Mast Cells and Potential Impact in Mastocytosis
Review

Response Criteria in Advanced Systemic Mastocytosis: Evolution in the Era of KIT Inhibitors

Division of Hematology, School of Medicine, Stanford Cancer Institute/Stanford University, 875 Blake Wilbur Drive, Stanford, CA 94305-6555, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Simona Soverini
Int. J. Mol. Sci. 2021, 22(6), 2983; https://doi.org/10.3390/ijms22062983
Received: 7 February 2021 / Revised: 11 March 2021 / Accepted: 12 March 2021 / Published: 15 March 2021
Systemic mastocytosis (SM) is a rare clonal hematologic neoplasm, driven, in almost all cases, by the activating KIT D816V mutation that leads to the growth and accumulation of neoplastic mast cells. While patients with advanced forms of SM have a poor prognosis, the introduction of KIT inhibitors (e.g., midostaurin, and avapritinib) has changed their outlook. Because of the heterogenous nature of advanced SM (advSM), successive iterations of response criteria have tried to capture different dimensions of the disease, including measures of mast cell burden (percentage of bone marrow mast cells and serum tryptase level), and mast cell-related organ damage (referred to as C findings). Historically, response criteria have been anchored to reversion of one or more organ damage finding(s) as a minimal criterion for response. This is a central principle of the Valent criteria, Mayo criteria, and International Working Group-Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis (IWG-MRT-ECNM) consensus criteria. Irrespective of the response criteria, an ever-present challenge is how to apply response criteria in patients with SM and an associated hematologic neoplasm, where the presence of both diseases complicates assignment of organ damage and adjudication of response. In the context of trials with the selective KIT D816V inhibitor avapritinib, pure pathologic response (PPR) criteria, which rely solely on measures of mast cell burden and exclude consideration of organ damage findings, are being explored as more robust surrogate of overall survival. In addition, the finding that avapritinib can elicit complete molecular responses of KIT D816V allele burden, establishes a new benchmark for advSM and motivates the inclusion of definitions for molecular response in future criteria. Herein, we also outline how the concept of PPR can inform a proposal for new response criteria which use a tiered evaluation of pathologic, molecular, and clinical responses. View Full-Text
Keywords: systemic mastocytosis; KIT D816V; midostaurin; avapritinib; IWG-MRT-ECNM systemic mastocytosis; KIT D816V; midostaurin; avapritinib; IWG-MRT-ECNM
Show Figures

Figure 1

MDPI and ACS Style

Shomali, W.; Gotlib, J. Response Criteria in Advanced Systemic Mastocytosis: Evolution in the Era of KIT Inhibitors. Int. J. Mol. Sci. 2021, 22, 2983. https://doi.org/10.3390/ijms22062983

AMA Style

Shomali W, Gotlib J. Response Criteria in Advanced Systemic Mastocytosis: Evolution in the Era of KIT Inhibitors. International Journal of Molecular Sciences. 2021; 22(6):2983. https://doi.org/10.3390/ijms22062983

Chicago/Turabian Style

Shomali, William, and Jason Gotlib. 2021. "Response Criteria in Advanced Systemic Mastocytosis: Evolution in the Era of KIT Inhibitors" International Journal of Molecular Sciences 22, no. 6: 2983. https://doi.org/10.3390/ijms22062983

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop