NCCN Guidelines® Insights: Systemic Mastocytosis, Version 3.2024

Featured Updates to the NCCN Guidelines

Authors:
Jason Gotlib Stanford Cancer Institute

Search for other papers by Jason Gotlib in
Current site
Google Scholar
PubMed
Close
 MD, MS
,
Aaron T. Gerds Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute

Search for other papers by Aaron T. Gerds in
Current site
Google Scholar
PubMed
Close
 MD, MS
,
Peter Abdelmessieh Fox Chase Cancer Center

Search for other papers by Peter Abdelmessieh in
Current site
Google Scholar
PubMed
Close
 DO, MSc
,
Haris Ali City of Hope National Medical Center

Search for other papers by Haris Ali in
Current site
Google Scholar
PubMed
Close
 MD
,
Mariana Castells Dana-Farber/Brigham and Women’s Cancer Center

Search for other papers by Mariana Castells in
Current site
Google Scholar
PubMed
Close
 MD, PhD
,
Andrew Dunbar Memorial Sloan Kettering Cancer Center

Search for other papers by Andrew Dunbar in
Current site
Google Scholar
PubMed
Close
 MD
,
Ruth Fein Revell Patient Advocate

Search for other papers by Ruth Fein Revell in
Current site
Google Scholar
PubMed
Close
 BS
,
Tracy I. George Huntsman Cancer Institute at the University of Utah

Search for other papers by Tracy I. George in
Current site
Google Scholar
PubMed
Close
 MD
,
Steven Green Roswell Park Comprehensive Cancer Center

Search for other papers by Steven Green in
Current site
Google Scholar
PubMed
Close
 MD
,
Krishna Gundabolu Fred & Pamela Buffett Cancer Center

Search for other papers by Krishna Gundabolu in
Current site
Google Scholar
PubMed
Close
 MBBS, MS
,
Elizabeth Hexner Abramson Cancer Center at the University of Pennsylvania

Search for other papers by Elizabeth Hexner in
Current site
Google Scholar
PubMed
Close
 MD, MS
,
Tania Jain The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Search for other papers by Tania Jain in
Current site
Google Scholar
PubMed
Close
 MBBS
,
Catriona Jamieson UC San Diego Moores Cancer Center

Search for other papers by Catriona Jamieson in
Current site
Google Scholar
PubMed
Close
 MD, PhD
,
Paul R. Kaesberg UC Davis Comprehensive Cancer Center

Search for other papers by Paul R. Kaesberg in
Current site
Google Scholar
PubMed
Close
 MD
,
Andrew T. Kuykendall Moffitt Cancer Center

Search for other papers by Andrew T. Kuykendall in
Current site
Google Scholar
PubMed
Close
 MD
,
Yazan Madanat UT Southwestern Simmons Comprehensive Cancer Center

Search for other papers by Yazan Madanat in
Current site
Google Scholar
PubMed
Close
 MD
,
Naveen Manchanda Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Search for other papers by Naveen Manchanda in
Current site
Google Scholar
PubMed
Close
 MD
,
Lucia Masarova The University of Texas MD Anderson Cancer Center

Search for other papers by Lucia Masarova in
Current site
Google Scholar
PubMed
Close
 MD
,
Jori May O’Neal Comprehensive Cancer Center at UAB

Search for other papers by Jori May in
Current site
Google Scholar
PubMed
Close
 MD
,
Brandon McMahon University of Colorado Cancer Center

Search for other papers by Brandon McMahon in
Current site
Google Scholar
PubMed
Close
 MD
,
Sanjay R. Mohan Vanderbilt-Ingram Cancer Center

Search for other papers by Sanjay R. Mohan in
Current site
Google Scholar
PubMed
Close
 MD, MSCI
,
Kalyan V. Nadiminti University of Wisconsin Carbone Cancer Center

Search for other papers by Kalyan V. Nadiminti in
Current site
Google Scholar
PubMed
Close
 MD
,
Stephen Oh Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Search for other papers by Stephen Oh in
Current site
Google Scholar
PubMed
Close
 MD, PhD
,
Jeanne Palmer Mayo Clinic Comprehensive Cancer Center

Search for other papers by Jeanne Palmer in
Current site
Google Scholar
PubMed
Close
 MD
,
Ami Patel Huntsman Cancer Institute at the University of Utah

Search for other papers by Ami Patel in
Current site
Google Scholar
PubMed
Close
 MD
,
Anand A. Patel The UChicago Medicine Comprehensive Cancer Center

Search for other papers by Anand A. Patel in
Current site
Google Scholar
PubMed
Close
 MD
,
Nikolai Podoltsev Yale Cancer Center/Smilow Cancer Hospital

Search for other papers by Nikolai Podoltsev in
Current site
Google Scholar
PubMed
Close
 MD, PhD
,
Lindsay Rein Duke Cancer Institute

Search for other papers by Lindsay Rein in
Current site
Google Scholar
PubMed
Close
 MD
,
Rachel Salit Fred Hutchinson Cancer Center

Search for other papers by Rachel Salit in
Current site
Google Scholar
PubMed
Close
 MD
,
Moshe Talpaz University of Michigan Rogel Cancer Center

Search for other papers by Moshe Talpaz in
Current site
Google Scholar
PubMed
Close
 MD
,
Martha Wadleigh Dana-Farber/Brigham and Women’s Cancer Center

Search for other papers by Martha Wadleigh in
Current site
Google Scholar
PubMed
Close
 MD
,
Sarah Wall The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute

Search for other papers by Sarah Wall in
Current site
Google Scholar
PubMed
Close
 MD, MPH
,
Mary Anne Bergman National Comprehensive Cancer Network

Search for other papers by Mary Anne Bergman in
Current site
Google Scholar
PubMed
Close
, and
Cindy Hochstetler National Comprehensive Cancer Network

Search for other papers by Cindy Hochstetler in
Current site
Google Scholar
PubMed
Close
 PhD
Restricted access

Mastocytosis is a heterogeneous group of disorders comprising cutaneous mastocytosis, systemic mastocytosis, and mast cell sarcoma. It is associated with a variety of symptoms related to the release of mast cell mediators and mast cell tissue infiltration. Referral to specialized centers with expertise in the management of mastocytosis and multidisciplinary collaboration with subspecialists (eg, allergists for the management of anaphylaxis and drug hypersensitivities, anesthesiologists for invasive procedures or surgery, high-risk obstetrician for pregnancy) is recommended. The NCCN Guidelines for Systemic Mastocytosis provide evidence- and consensus-based recommendations for the diagnosis and comprehensive care of patients with systemic mastocytosis. The multidisciplinary panel of experts convenes at least once a year to review requested changes to the guidelines from both internal and external entities as well as to discuss data on existing and new therapies. These NCCN Guidelines Insights focus on some of the recent updates to the guidelines.

  • Collapse
  • Expand
  • 1.

    Valent P, Horny HP, Escribano L, et al. Diagnostic criteria and classification of mastocytosis: a consensus proposal. Leuk Res 2001;25:603625.

  • 2.

    Swerdlow SH, Campo E, Harris NL, et al. eds, WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th ed. International Agency for Research on Cancer; 2017.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Arber DA, Orazi A, Hasserjian RP, et al. International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data. Blood 2022;140:12001228.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: myeloid and histiocytic/dendritic neoplasms. Leukemia 2022;36:17031719.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    El Hussein S, Chifotides HT, Khoury JD, et al. Systemic mastocytosis and other entities involving mast cells: a practical review and update. Cancers (Basel) 2022;14:3474.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Gotlib J, Castells M, Oude Elberink H, et al. Avapritinib versus placebo in indolent systemic mastocytosis. NEJM Evid 2023;2:EVIDoa2200339.

  • 7.

    Kluin-Nelemans HC, Oldhoff JM, Van Doormaal JJ, et al. Cladribine therapy for systemic mastocytosis. Blood 2003;102:42704276.

  • 8.

    Lim KH, Pardanani A, Butterfield JH, et al. Cytoreductive therapy in 108 adults with systemic mastocytosis: outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine. Am J Hematol 2009;84:790794.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Barete S, Lortholary O, Damaj G, et al. Long-term efficacy and safety of cladribine (2-CdA) in adult patients with mastocytosis. Blood 2015;126:10091016; quiz 1050.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Delaporte E, Piérard E, Wolthers BG, et al. Interferon-alpha in combination with corticosteroids improves systemic mast cell disease. Br J Dermatol 1995;132:479482.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Casassus P, Caillat-Vigneron N, Martin A, et al. Treatment of adult systemic mastocytosis with interferon-alpha: results of a multicentre phase II trial on 20 patients. Br J Haematol 2002;119:10901097.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Hauswirth AW, Simonitsch-Klupp I, Uffmann M, et al. Response to therapy with interferon alpha-2b and prednisolone in aggressive systemic mastocytosis: report of five cases and review of the literature. Leuk Res 2004;28:249257.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Simon J, Lortholary O, Caillat-Vigneron N, et al. Interest of interferon alpha in systemic mastocytosis. The French experience and review of the literature. Pathol Biol (Paris) 2004;52:294299.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Castells M, Butterfield J. Mast cell activation syndrome and mastocytosis: initial treatment options and long-term management. J Allergy Clin Immunol Pract 2019;7:10971106.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    DeAngelo DJ, Radia DH, George TI, et al. Safety and efficacy of avapritinib in advanced systemic mastocytosis: the phase 1 EXPLORER trial. Nat Med 2021;27:21832191.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Gotlib J, Reiter A, Radia DH, et al. Efficacy and safety of avapritinib in advanced systemic mastocytosis: interim analysis of the phase 2 PATHFINDER trial. Nat Med 2021;27:21922199.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Gotlib J, Kluin-Nelemans HC, George TI, et al. Efficacy and safety of midostaurin in advanced systemic mastocytosis. N Engl J Med 2016;374:25302541.

  • 18.

    Chandesris MO, Damaj G, Canioni D, et al. Midostaurin in advanced systemic mastocytosis. N Engl J Med 2016;374:26052607.

  • 19.

    DeAngelo DJ, George TI, Linder A, et al. Efficacy and safety of midostaurin in patients with advanced systemic mastocytosis: 10-year median follow-up of a phase II trial. Leukemia 2018;32:470478.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Frost MJ, Ferrao PT, Hughes TP, et al. Juxtamembrane mutant V560GKit is more sensitive to imatinib (STI571) compared with wild-type c-kit whereas the kinase domain mutant D816VKit is resistant. Mol Cancer Ther 2002;1:11151124.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Akin C, Brockow K, D’Ambrosio C, et al. Effects of tyrosine kinase inhibitor STI571 on human mast cells bearing wild-type or mutated c-kit. Exp Hematol 2003;31:686692.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Akin C, Fumo G, Yavuz AS, et al. A novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib. Blood 2004;103:32223225.

  • 23.

    Zhang LY, Smith ML, Schultheis B, et al. A novel K509I mutation of KIT identified in familial mastocytosis-in vitro and in vivo responsiveness to imatinib therapy. Leuk Res 2006;30:373378.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Heinrich MC, Joensuu H, Demetri GD, et al. Phase II, open-label study evaluating the activity of imatinib in treating life-threatening malignancies known to be associated with imatinib-sensitive tyrosine kinases. Clin Cancer Res 2008;14:27172725.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Vega-Ruiz A, Cortes JE, Sever M, et al. Phase II study of imatinib mesylate as therapy for patients with systemic mastocytosis. Leuk Res 2009;33:14811484.

  • 26.

    Mital A, Piskorz A, Lewandowski K, et al. A case of mast cell leukaemia with exon 9 KIT mutation and good response to imatinib. Eur J Haematol 2011;86:531535.

  • 27.

    Alvarez-Twose I, Matito A, Morgado JM, et al. Imatinib in systemic mastocytosis: a phase IV clinical trial in patients lacking exon 17 KIT mutations and review of the literature. Oncotarget 2016;8:6895068963.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Reiter A, Gotlib J, Álvarez-Twose I, et al. Efficacy of avapritinib versus best available therapy in the treatment of advanced systemic mastocytosis. Leukemia 2022;36:21082120.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Reiter A, Gotlib J, Alvarez Twose I, et al. Overall survival in patients with advanced systemic mastocytosis receiving avapritinib versus midostaurin or cladribine. Hemasphere 2022;6(Suppl):Abstract P1014.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Reiter A, Gotlib J, Alvarez Twose I, et al. Overall survival in patients with systemic mastocytosis with associated hematologic neoplasm treated with avapritinib versus best available therapy. Hemasphere 2022;6(Suppl):Abstract P1013.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Reiter A, Schwaab J, DeAngelo DJ, et al. Efficacy and safety of avapritinib in previously treated patients with advanced systemic mastocytosis. Blood Adv 2022;6:57505762.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    van Anrooij B, Oude Elberink JN, Span LFR, et al. Midostaurin in patients with indolent systemic mastocytosis: an open-label phase 2 trial. J Allergy Clin Immunol 2018;142:10061008.e7.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Jawhar M, Schwaab J, Naumann N, et al. Response and progression on midostaurin in advanced systemic mastocytosis: KIT D816V and other molecular markers. Blood 2017;130:137145.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Hartmann K, Gotlib J, Akin C, et al. Midostaurin improves quality of life and mediator-related symptoms in advanced systemic mastocytosis. J Allergy Clin Immunol 2020;146:356366.e4.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Pardanani A, Ketterling RP, Brockman SR, et al. CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy. Blood 2003;102:30933096.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Pardanani A, Brockman SR, Paternoster SF, et al. FIP1L1-PDGFRA fusion: prevalence and clinicopathologic correlates in 89 consecutive patients with moderate to severe eosinophilia. Blood 2004;104:30383045.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Przepiorka D, Giralt S, Khouri I, et al. Allogeneic marrow transplantation for myeloproliferative disorders other than chronic myelogenous leukemia: review of forty cases. Am J Hematol 1998;57:2428.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Nakamura R, Chakrabarti S, Akin C, et al. A pilot study of nonmyeloablative allogeneic hematopoietic stem cell transplant for advanced systemic mastocytosis. Bone Marrow Transplant 2006;37:353358.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Ustun C, Reiter A, Scott BL, et al. Hematopoietic stem-cell transplantation for advanced systemic mastocytosis. J Clin Oncol 2014;32:32643274.

  • 40.

    McLornan DP, Czerw T, Damaj G, et al. Allogeneic haematopoietic cell transplantation for advanced systemic mastocytosis: best practice recommendations on behalf of the EBMT Practice Harmonisation and Guidelines Committee. Leukemia 2024;38:699711.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41.

    Ustun C, Gotlib J, Popat U, et al. Consensus opinion on allogeneic hematopoietic cell transplantation in advanced systemic mastocytosis. Biol Blood Marrow Transplant 2016;22:13481356.

    • PubMed
    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 1978 1978 1175
PDF Downloads 1381 1381 859
EPUB Downloads 0 0 0