544
Views
0
CrossRef citations to date
0
Altmetric
Review

Systemic mastocytosis: 2023 update on diagnosis and management in adults

, , , , , , , ORCID Icon & ORCID Icon show all
Pages 153-165 | Received 11 Apr 2023, Accepted 30 May 2023, Published online: 06 Jun 2023

References

  • Valent P, Akin C, Metcalfe DD. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts. Blood. 2017;129:1420–1427.
  • Krystel-Whittemore M, Dileepan KN, Wood JG. Mast cell: a multi-functional master cell. Front Immunol. 2016;6. [[cited 2023 Mar 1]]. InternetAvailable from: http://journal.frontiersin.org/Article/10.3389/fimmu.2015.00620/abstract
  • Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–2405.
  • 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;140:1200–1228.
  • Lim K-H, Tefferi A, Lasho TL, et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood. 2009;113:5727–5736.
  • Castells M, Metcalfe DD, Escribano L. Diagnosis and treatment of cutaneous mastocytosis in children: practical recommendations. Am J Clin Dermatol. 2011;12:259–270.
  • Castells M, Butterfield J. Mast cell activation syndrome and mastocytosis: initial treatment options and long-term management. J Allergy Clin Immunol Pract. 2019;7:1097–1106.
  • Castells M, KF A. Mastocytosis: mediator-related signs and symptoms. Int Arch Allergy Immunol. 2002;127:147–152.
  • Gülen T, Akin C, Bonadonna P, et al. Selecting the right criteria and proper classification to diagnose mast cell activation syndromes: a critical review. J Allergy Clin Immunol Pract. 2021;9:3918–3928.
  • Valent P, Hartmann K, Bonadonna P, et al. Mast cell activation syndromes: collegium internationale allergologicum update 2022. Int Arch Allergy Immunol. 2022;183:693–705.
  • Horny H-P, Valent P. Histopathological and immunohistochemical aspects of mastocytosis. Int Arch Allergy Immunol. 2002;127:115–117.
  • Valent P, Sperr WR, Sotlar K, et al. The serum tryptase test: an emerging robust biomarker in clinical hematology. Expert Rev Hematol. 2014;7:683–690.
  • Greiner G, Sprinzl B, Gisslinger B, et al. Hereditary a tryptasemia is a valid genetic biomarker for severe mediator-related symptoms in mastocytosis. Blood. 2021;137(2):238–247. doi: 10.1182/blood.2020006157
  • Lyons JJ, Chovanec J, O’Connell MP, et al. Heritable risk for severe anaphylaxis associated with increased α-tryptase–encoding germline copy number at TPSAB1. J Allergy Clin Immunol. 2021;147:622–632.
  • Valent P, Akin C, Hartmann K, et al. Updated diagnostic criteria and classification of mast cell disorders: a consensus proposal. Hemasphere. 2021;5:e646.
  • Lyman SD, Jacobsen SEW. C-kit ligand and Flt3 Ligand: stem/progenitor cell factors with overlapping yet distinct activities. Blood. 1998;91:1101–1134.
  • Clark SC, Sprinzl B, Górska A. Hereditary α tryptasemia is a valid genetic biomarker for severe mediator-related symptoms in mastocytosis. Blood. 2021;137:238–247.
  • Reith AD, Ellis C, Lyman SD, et al. Signal transduction by normal isoforms and W mutant variants of the Kit receptor tyrosine kinase. Embo J. 1991;10:2451–2459.
  • Arock M, Hoermann G, Sotlar K, et al. Clinical impact and proposed application of molecular markers, genetic variants, and cytogenetic analysis in mast cell neoplasms: status 2022. J Allergy Clin Immunol. 2022;149:1855–1865.
  • Valent P, Akin C, Sperr WR, et al. New insights into the pathogenesis of mastocytosis: emerging concepts in diagnosis and therapy. Annu Rev Pathol Mech Dis. 2023;18:361–386.
  • Tanasi I, Bonifacio M, Pizzolato M, et al. Familial occurrence of systemic and cutaneous mastocytosis in an adult multicentre series. Br J Haematol. 2021;193:845–848.
  • Pardanani A, Lasho T, Elala Y, et al. Next-generation sequencing in systemic mastocytosis: derivation of a mutation-augmented clinical prognostic model for survival: prognostic model for survival in systemic mastocytosis. Am J Hematol. 2016;91:888–893.
  • Schwaab J, Schnittger S, Sotlar K, et al. Comprehensive mutational profiling in advanced systemic mastocytosis. Blood. 2013;122:2460–2466.
  • Arock M, Sotlar K, Akin C, et al. KIT mutation analysis in mast cell neoplasms: recommendations of the European competence network on mastocytosis. Leukemia. 2015;29:1223–1232.
  • Tefferi A, Levine RL, Lim K-H, et al. Frequent TET2 mutations in systemic mastocytosis: clinical, KITD816V and FIP1L1-PDGFRA correlates. Leukemia. 2009;23:900–904.
  • 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;36:1703–1719.
  • Zanotti R, Tanasi I, Bernardelli A, et al. Bone marrow mastocytosis: a diagnostic challenge. J Clin Med. 2021;10:1420.
  • Sotlar K, Colak S, Bache A, et al. Variable presence of KIT D816V in clonal haematological non-mast cell lineage diseases associated with systemic mastocytosis (SM-AHNMD). J Pathol. 2010;220:586–595.
  • Wang SA, Hutchinson L, Tang G, et al. Systemic mastocytosis with associated clonal hematological non-mast cell lineage disease: clinical significance and comparison of chomosomal abnormalities in SM and AHNMD components. Am J Hematol. 2013;88:219–224.
  • Valent P, Sotlar K, Sperr WR, et al. Chronic mast cell leukemia: a novel leukemia-variant with distinct morphological and clinical features. Leuk Res. 2015;39:1–5.
  • Álvarez-Twose I, Jara-Acevedo M, Morgado JM, et al. Clinical, immunophenotypic, and molecular characteristics of well-differentiated systemic mastocytosis. J Allergy Clin Immunol. 2016;137:168–178.e1.
  • Huang L, Wang SA, Konoplev S, et al. Well-differentiated systemic mastocytosis showed excellent clinical response to imatinib in the absence of known molecular genetic abnormalities: a case report. Medicine (Baltimore). 2016;95:e4934.
  • Pieri L, Bonadonna P, Elena C, et al. Clinical presentation and management practice of systemic mastocytosis. A survey on 460 Italian patients: a Survey on 460 patients with systemic mastocytosis. Am J Hematol. 2016;91:692–699.
  • Trizuljak J, Sperr WR, Nekvindová L, et al. Clinical features and survival of patients with indolent systemic mastocytosis defined by the updated WHO classification. Allergy. 2020;75:1927–1938.
  • Valent P, Hartmann K, Schwaab J, et al. Personalized management strategies in mast cell disorders: eCNM-AIM user’s guide for daily clinical practice. J Allergy Clin Immunol Pract. 2022;10:1999–2012.e6.
  • Aberer E, Sperr WR, Bretterklieber A, et al. Clinical impact of skin lesions in mastocytosis: a multicenter study of the European competence network on mastocytosis. J Invest Dermatol. 2021;141:1719–1727.
  • Escribano L, Álvarez-Twose I, Sánchez-Muñoz L, et al. Prognosis in adult indolent systemic mastocytosis: a long-term study of the Spanish Network on Mastocytosis in a series of 145 patients. J Allergy Clin Immunol. 2009;124:514–521.
  • Pardanani A, Tefferi A. Systemic mastocytosis in adults: a review on prognosis and treatment based on 342 Mayo Clinic patients and current literature. Curr Opin Hematol. 2010;17:125–132.
  • Zanotti R, Bonifacio M, Lucchini G, et al. Refined diagnostic criteria for bone marrow mastocytosis: a proposal of the European competence network on mastocytosis. Leukemia. 2022;36:516–524.
  • Pardanani A, Shah S, Mannelli F, et al. Mayo alliance prognostic system for mastocytosis: clinical and hybrid clinical-molecular models. Blood Adv. 2018;2:2964–2972.
  • Pardanani A, Lasho TL, Reichard KK, et al. World Health Organization class-independent risk categorization in mastocytosis. Blood Cancer J. 2019;9:1–3.
  • Sperr WR, Kundi M, Alvarez-Twose I, et al. International prognostic scoring system for mastocytosis (IPSM): a retrospective cohort study. Lancet Haematol. 2019;6:e638–e649.
  • Muñoz-González JI, Álvarez-Twose I, Jara-Acevedo M, et al. Proposed global prognostic score for systemic mastocytosis: a retrospective prognostic modelling study. Lancet Haematol. 2021;8:e194–e204.
  • Jawhar M, Schwaab J, Álvarez-Twose I, et al. MARS: mutation-adjusted risk score for advanced systemic mastocytosis. J Clin Oncol. 2019;37:2846–2856.
  • Pardanani A. How I treat patients with indolent and smoldering mastocytosis (rare conditions but difficult to manage). Blood. 2013;121:3085–3094.
  • Carter MC, Robyn JA, Bressler PB, et al. Omalizumab for the treatment of unprovoked anaphylaxis in patients with systemic mastocytosis. J Allergy Clin Immunol. 2007;119:1550–1551.
  • Jendoubi F, Gaudenzio N, Gallini A, et al. Omalizumab in the treatment of adult patients with mastocytosis: a systematic review. Clin Exp Allergy. 2020;50:654–661.
  • 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;84:790–794.
  • Available and emerging therapies for bona fide advanced systemic mastocytosis and primary eosinophilic neoplasms. Hematology, ASH Education Program American Society of Hematology [Internet]. [cited 2023 Mar 15]. Available from: https://ashpublications.org/hematology/article/2022/1/34/493554/Available-and-emerging-therapies-for-bona-fide
  • 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;32:470–478.
  • van Anrooij B, Oude Elberink JNG, Span LFR, et al. Midostaurin in patients with indolent systemic mastocytosis: an open-label phase 2 trial. J Allergy Clin Immunol. 2018;142:1006–1008.e7.
  • 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;27:2183–2191.
  • Radia D Avapritinib as first-line therapy in patients with advanced systemic mastocytosis: efficacy and safety from the pathfinder clinical study. ASH; 2022 [cited 2023 Mar 12]. Available from: https://ash.confex.com/ash/2022/webprogram/Paper166986.html
  • Akin C Results from pioneer: a randomized, double-blind, placebo-controlled, phase 2 study of avapritinib in patients with indolent systemic mastocytosis. ASH; 2020 [cited 2023 Mar 12]. Available from: https://ash.confex.com/ash/2020/webprogram/Paper139367.html.
  • Additional PIONEER study results back FDA priority review for avapritinib in indolent systemic mastocytosis [Internet]. Target. Oncol. 2023 [cited 2023 Mar 12]. Available from: https://www.targetedonc.com/view/additional-pioneer-study-results-back-fda-priority-review-for-avapritinib-in-indolent-systemic-mastocytosis
  • Droogendijk HJ, Kluin-Nelemans HJC, van Doormaal JJ, et al. Imatinib mesylate in the treatment of systemic mastocytosis: a phase II trial. Cancer. 2006;107:345–351.
  • 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;33:1481–1484.
  • 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. 2017;8:68950–68963.
  • Paul C, Sans B, Suarez F, et al. Masitinib for the treatment of systemic and cutaneous mastocytosis with handicap: a phase 2a study. Am J Hematol. 2010;85:921–925.
  • Lortholary O, Chandesris MO, Livideanu CB, et al. Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study. Lancet. 2017;389:612–620.
  • Ustun C, Gotlib J, Popat U, et al. Consensus opinion on allogeneic hematopoietic cell transplantation in advanced systemic mastocytosis. Biol Blood Marrow Transplant. 2016;22:1348–1356.
  • Schlenk RF, Kayser S. Midostaurin: a multiple tyrosine kinases inhibitor in acute myeloid leukemia and systemic mastocytosis. In: Martens U, editor. Small mol hematol [Internet]. Cham: Springer International Publishing; 2018[cited 2023 Feb 22]; p. 199–214. Available from: http://link.springer.com/10.1007/978-3-319-91439-8_10
  • Gotlib J, Kluin-Nelemans HC, George TI, et al. Efficacy and safety of midostaurin in advanced systemic mastocytosis. N Engl J Med. 2016;374:2530–2541.
  • Singh A, Al‐Kali A, Begna KH, et al. Midostaurin therapy for advanced systemic mastocytosis: mayo Clinic experience in 33 consecutive cases. Am J Hematol. 2022;97:630–637.
  • Papayannidis C Real-World management of advanced systemic mastocytosis treated with midostaurin: analysis of patients who completed 12 months of follow-up from an Italian observational study (OVIDIO). ASH; 2022 [cited 2023 Mar 11]. Available from: https://ash.confex.com/ash/2022/webprogram/Paper156371.html.
  • Farrukh F, Gangat N, Shah MV, et al. Midostaurin therapy for indolent and smoldering systemic mastocytosis: retrospective review of Mayo Clinic experience. Am J Hematol. 2022;97 [[cited 2023 Mar 12]]. InternetAvailable from: https://onlinelibrary.wiley.com/doi/10.1002/ajh.26464
  • Gotlib J, Reiter A, DeAngelo DJ. Avapritinib for advanced systemic mastocytosis. Blood. 2022;140:1667–1673.
  • Reiter A, Schwaab J, DeAngelo DJ, et al. Efficacy and safety of avapritinib in previously treated patients with advanced systemic mastocytosis. Blood Adv. 2022;6:5750–5762.
  • Rong L, Xie M, Jiang M, et al. A post‐marketing pharmacovigilance study of avapritinib: adverse event data mining and analysis based on the United States food and drug administration adverse event reporting system database. Br J Clin Pharmacol. 2023; bcp.15673. doi: 10.1111/bcp.15673
  • Akin C, Arock M, Valent P. Tyrosine kinase inhibitors for the treatment of indolent systemic mastocytosis: are we there yet? J Allergy Clin Immunol. 2022;149:1912–1918.
  • Akin C, Metcalfe DD. The biology of Kit in disease and the application of pharmacogenetics. J Allergy Clin Immunol. 2004;114:13–19.
  • Pardanani A, Elliott M, Reeder T, et al. Imatinib for systemic mast-cell disease. Lancet. 2003;362:535–537.
  • Valent P, Akin C, Hartmann K, et al. Drug-induced mast cell eradication: a novel approach to treat mast cell activation disorders? J Allergy Clin Immunol. 2022;149:1866–1874.
  • Rymut SM, Sukumaran S, Sperinde G, et al. Dose‐dependent inactivation of airway tryptase with a novel dissociating anti‐tryptase antibody (MTPS9579A) in healthy participants: a randomized trial. Clin Transl Sci. 2022;15:451–463.
  • Alvarado D, Maurer M, Gedrich R, et al. Anti‐KIT monoclonal antibody CDX‐0159 induces profound and durable mast cell suppression in a healthy volunteer study. Allergy. 2022;77:2393–2403.
  • Chang H-W, Sim K-H, Lee Y-J. Thalidomide attenuates mast cell activation by upregulating SHP-1 signaling and interfering with the action of CRBN. Cells. 2023;12:469.
  • Dave N, Devlin M, Rodstrom J, et al. Abstract CT122: safety and pharmacokinetics of BLU-263, a next-generation KIT inhibitor, in normal healthy volunteers. Cancer Res. 2021;81:CT122–CT122. CT122. doi: 10.1158/1538-7445.AM2021-CT122
  • Castells M, Scherber R, Bhavsar V, et al. P1017: hARBOR: a PHASE 2/3 STUDY of BLU-263 in PATIENTS with INDOLENT SYSTEMIC MASTOCYTOSIS and MONOCLONAL MAST CELL ACTIVATION SYNDROME. Hemasphere. 2022;6:907.
  • DeAngelo DJ, Reiter A, George TI, et al. AZURE: a phase 1/2 study of Blu-263 as monotherapy and in combination with azacitidine in patients with advanced systemic mastocytosis. Blood. 2022;140:6877–6878.
  • Akin C Summit: a 3-part, phase 2 study of Bezuclastinib (CGT9486), an Oral, selective, and potent KIT D816V Inhibitor, in adult patients with nonadvanced systemic mastocytosis (NonAdvsm). ASH; 2022 [cited 2023 Mar 14]. Available from: https://ash.confex.com/ash/2022/webprogram/Paper156326.html
  • DeAngelo DJ, Pullarkat VA, Piris-Villaespesa M, et al. Preliminary safety and efficacy from Apex, a phase 2 study of Bezuclastinib (CGT9486), a Novel, Highly selective, potent KIT D816V Tyrosine Kinase inhibitor, in adults with advanced systemic mastocytosis (AdvSM). Blood. 2022;140:1512–1513.
  • Guarnieri A, Chicarelli M, Cable L, et al. Preclinical Data with KIT D816V inhibitor Bezuclastinib (CGT9486) demonstrates high selectivity and minimal brain penetrance. Blood. 2021;138:4595–4595.
  • Schneeweiss M, Peter B, Bibi S, et al. The KIT and PDGFRA switch-control inhibitor DCC-2618 blocks growth and survival of multiple neoplastic cell types in advanced mastocytosis. Haematologica. 2018;103:799–809.
  • Hilberg F, Roth GJ, Krssak M, et al. BIBF 1120: triple Angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008;68:4774–4782.
  • Toledo MAS, Gatz M, Sontag S, et al. Nintedanib targets KIT D816V neoplastic cells derived from induced pluripotent stem cells of systemic mastocytosis.
  • Degenfeld-Schonburg L, Gamperl S, Stefanzl G, et al. Antineoplastic efficacy profiles of avapritinib and nintedanib in KIT D816V+ systemic mastocytosis: a preclinical study. Am J Cancer Res. 2003;13(2):355–378.
  • Jennings SV, Slee VM, Zack RM, et al. Patient perceptions in mast cell disorders. Immunol Allergy Clin North Am. 2018;38:505–525.
  • Hoermann G, Sotlar K, Jawhar M, et al. Standards of genetic testing in the diagnosis and prognostication of systemic mastocytosis in 2022: recommendations of the EU-US cooperative group. J Allergy Clin Immunol Pract. 2022;10:1953–1963.
  • Boggs NA, Sun X, Lyons JJ, et al. Challenges in applying diagnostic criteria for systemic mastocytosis. Blood Adv. 2023.
  • Monaldi C, de Santis S, Mancini M, et al. MPN-182 droplet digital PCR for non-invasive detection of the KIT D816V mutation in the peripheral blood of patients with suspected systemic mastocytosis. Clin Lymphoma Myeloma Leuk. 2022;22:S328.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.