Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Sep 11:15:421-433.
doi: 10.2147/JBM.S366367. eCollection 2024.

Management of Advanced Systemic Mastocytosis: Clinical Challenges

Douglas Tremblay  1 , Nicole E Wagner  2 , John Mascarenhas  1
Affiliations
Review

Management of Advanced Systemic Mastocytosis: Clinical Challenges

Douglas Tremblay et al. J Blood Med. .

Abstract

Advanced systemic mastocytosis (AdvSM) is a rare hematologic malignancy with organ damage and compromised life expectancy arising from organ accumulation of neoplastic mast cells. Identification of the gain-of-function KITD816V in the majority of cases has accelerated pharmaceutical development culminating with the development of selective KIT inhibitors such as avapritinib. While the advent of these therapies has improved the quality and quantity of life in patients with AdvSM, current challenges remain in the management of this disease. In this review, we summarize the present and future therapeutics landscape of AdvSM, highlighting the development of novel KIT inhibitors including elenestinib and bezuclastinib. We also explore the continued role of additional treatment modalities including allogeneic stem cell transplantation before discussing unresolved clinical challenges in the management of AdvSM.

Keywords: KITD816V; avapritinib; midostaurin; systemic mastocytosis.

PubMed Disclaimer

Conflict of interest statement

DT received research funding from Sobi, Sumitomo, Cogent Biosciences and Gilead and honoraria from Sobi, Novartis, AbbVie, PharmaEssentia, Sierra Oncology, GSK and Cogent Biosciences. JM received research funding from Incyte, BMS, Novartis, AbbVie, Geron, Kartos, Karyopharm, CTI/Sobi and PharmaEssentia and honoraria from Incyte, Blueprint Medicines, Keros, DISC Medicines, BMS, AbbVie, Kartos, Geron, GSK, Roche, Merck, Pfizer, PharmaEssentia, MorphoSys, Novartis, Galecto, Sobi, Sumitomo, and Karyopharm. The authors report no other conflicts of interest in this work.

References

    1. Bergstrom A, Hagglund H, Berglund A, Nilsson G, Lambe M. Epidemiology of mastocytosis: a population-based study (Sweden). Acta Oncol. 2024;63:44–50. doi:10.2340/1651-226X.2024.31406 - DOI - PMC - PubMed
    1. Rottem M, Kirshenbaum AS, Metcalfe DD. Early development of mast cells. Int Arch Allergy Appl Immunol. 1991;94(1–4):104–109. doi:10.1159/000235339 - DOI - PubMed
    1. Martelli M, Monaldi C, De Santis S, et al. Recent advances in the molecular biology of systemic mastocytosis: implications for diagnosis, prognosis, and therapy. Int J Mol Sci. 2020;21(11):3987. doi:10.3390/ijms21113987 - DOI - PMC - PubMed
    1. Nagata H, Worobec AS, Oh CK, et al. Identification of a point mutation in the catalytic domain of the protooncogene c-kit in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder. Proc Natl Acad Sci USA. 1995;92(23):10560–10564. doi:10.1073/pnas.92.23.10560 - DOI - PMC - PubMed
    1. Bibi S, Langenfeld F, Jeanningros S, et al. Molecular defects in mastocytosis: KIT and beyond KIT. Immunol Allergy Clin North Am. 2014;34(2):239–262. doi:10.1016/j.iac.2014.01.009 - DOI - PubMed

LinkOut - more resources