Recent advances in diagnosis and therapy in systemic mastocytosis

다국어 초록 (Multilingual Abstract)

Mastocytosis is a heterogeneous neoplasm characterized by accumulation of neoplastic mast cells in various organs. There are three main types: cutaneous mastocytosis (CM), systemic mastocytosis (SM), and mast cell sarcoma. CM mainly affects children and is confined to the skin, whereas SM affects adults and is characterized by extracutaneous involvement, with or without cutaneous involvement. Most cases of SM have an indolent clinical course; however, some types of SM have aggressive behavior and a poor prognosis. Recent advances in the understanding of the molecular changes in SM have changed the diagnosis and treatment of aggressive and advanced SM subtypes. The International Consensus Classification and World Health Organization refined the diagnostic criteria and classification of SM as a result of accumulation of clinical experience and advances in molecular diagnostics. Somatic mutations in the KIT gene, most frequently KIT D816V, are detected in 90% of patients with SM. Expression of CD30 and any KIT mutation were introduced as minor diagnostic criteria after the introduction of highly sensitive screening methods. SM has a wide spectrum of clinical features, and only a few drugs are effective at treating advanced SM. Currently, the mainstay of SM treatment is limited to the management of chronic symptoms related to release of mast cell mediators. Small-molecule kinase inhibitors targeting the KIT-downstream and KIT-independent pathways were recently approved for treating advanced SM. I describe recent advances in diagnosis of SM, and review the currently available and emerging therapeutic options for SM management.

참고문헌 (Reference)

• 1 Bischoff SC, "c-kit ligand : a unique potentiator of mediator release by human lung mast cells" 175 : 237-244, 1992
• 2 Pardanani A, "WHO subvariants of indolent mastocytosis : clinical details and prognostic evaluation in 159 consecutive adults" 115 : 150-151, 2010
• 3 Ellis JM, "Urticaria pigmentosa; a report of a case with autopsy" 48 : 426-435, 1949
• 4 Ustun C, "Tyrosine kinase inhibitors in the treatment of systemic mastocytosis" 35 : 1143-1152, 2011
• 5 Siebenhaar F, "Treatment strategies in mastocytosis" 34 : 433-447, 2014
• 6 Caplan RM, "The natural course of urticaria pigmentosa. Analysis and follow-up of 112 cases" 87 : 146-157, 1963
• 7 Ma Y, "The c-KIT mutation causing human mastocytosis is resistant to STI571 and other KIT kinase inhibitors; kinases with enzymatic site mutations show different inhibitor sensitivity profiles than wild-type kinases and those with regulatory-type mutations" 99 : 1741-1744, 2002
• 8 Erben P, "The KIT D816V expressed allele burden for diagnosis and disease monitoring of systemic mastocytosis" 93 : 81-88, 2014
• 9 Hoermann G, "The KIT D 816 V allele burden predicts survival in patients with mastocytosis and correlates with the WHO type of the disease" 69 : 810-813, 2014
• 10 Khoury JD, "The 5th edition of the World Health Organization classification of haematolymphoid tumours : myeloid and histiocytic/dendritic neoplasms" 36 : 1703-1719, 2022
• 11 Arber DA, "The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia" 127 : 2391-2405, 2016
• 12 National Comprehensive Cancer Network, "Systemic mastocytosis version 2.2022, NCCN clinical practice guidelines in oncology 2022. Plymouth Meeting" NCCN
• 13 Pardanani A, "Systemic mastocytosis in adults : 2012 update on diagnosis, risk stratification, and management" 87 : 401-411, 2012
• 14 Lim KH, "Systemic mastocytosis in 342consecutive adults : survival studies and prognostic factors" 113 : 5727-5736, 2009
• 15 Travis WD, "Systemic mast cell disease. Analysis of 58 cases and literature review" 67 : 345-368, 1988
• 16 Lübke J, "Superior efficacy of midostaurin over cladribine in advanced systemic mastocytosis : a registry-based analysis" 40 : 1783-1794, 2022
• 17 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)" 140 (140): 6838-6839, 2022
• 18 Valent P, "Standards and standardization in mastocytosis : consensus statements on diagnostics, treatment recommendations and response criteria" 37 : 435-453, 2007
• 19 Kristensen T, "Sensitive KIT D816V mutation analysis of blood as a diagnostic test in mastocytosis" 89 : 493-498, 2014
• 20 DeAngelo DJ, "Safety and efficacy of avapritinib in advanced systemic mastocytosis : the phase 1EXPLORER trial" 27 : 2183-2191, 2021
• 21 Jawhar M, "Response and progression on midostaurin in advanced systemic mastocytosis : KIT D816V and other molecular markers" 130 : 137-145, 2017
• 22 Nettleship E, "Rare form of urticaria" 2 : 323-324, 1869
• 23 Muñoz-González JI, "Proposed global prognostic score for systemic mastocytosis : a retrospective prognostic modelling study" 8 : e194-204, 2021
• 24 Valent P, "Proposed diagnostic algorithm for patients with suspected mastocytosis : a proposal of the European Competence Network on Mastocytosis" 69 : 1267-1274, 2014
• 25 Gotlib J, "Proposed European Competence Network on Mastocytosis—American Initiative in Mast Cell Diseases(ECNM-AIM)response criteria in advanced systemic mastocytosis" 10 : 2025-2038, 2022
• 26 DeAngelo DJ, "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)" 140 (140): 1512-1513, 2022
• 27 Akin C, "Pioneer part 2 : a randomized, double-blind, placebo-controlled, phase 2 study to evaluate safety and efficacy of avapritinib in indolent systemic mastocytosis" 136 (136): 1248-, 2020
• 28 Uzzaman A, "Pediatric-onset mastocytosis : a long term clinical follow-up and correlation with bone marrow histopathology" 53 : 629-634, 2009
• 29 Bodemer C, "Pediatric mastocytosis is a clonal disease associated with D816V and other activating c-KIT mutations" 130 : 804-815, 2010
• 30 Jawhar M, "Molecular profiling of myeloid progenitor cells in multi-mutated advanced systemic mastocytosis identifies KIT D816V as a distinct and late event" 29 : 1115-1122, 2015
• 31 Valent P, "Midostaurin : a magic bullet that blocks mast cell expansion and activation" 28 : 2367-2376, 2017
• 32 Pardanani A, "Mayo alliance prognostic system for mastocytosis : clinical and hybrid clinical-molecular models" 2 : 2964-2972, 2018
• 33 Soter NA, "Mastocytosis and the skin" 14 : 537-555, 2000
• 34 Valent P, "Mastocytosis : 2016 updated WHO classification and novel emerging treatment concepts" 129 : 1420-1427, 2017
• 35 Mekori YA, "Mast cells in innate immunity" 173 : 131-140, 2000
• 36 Jain P, "Mast cell leukemia(MCL) : clinico-pathologic and molecular features and survival outcome" 59 : 105-109, 2017
• 37 Kennedy VE, "Mast cell leukemia : clinical and molecular features and survival outcomes of patients in the ECNM registry" 2022
• 38 Akin C, "Mast cell activation syndrome : proposed diagnostic criteria" 126 : 1099-1104, 2010
• 39 Radia D, "MPN-395 : efficacy and safety of ≤ 200 mg avapritinib in patients with advanced systemic mastocytosis : pooled results from the phase 1EXPLORER and interim phase 2 PATHFINDER studies" 21 (21): S367-8, 2021
• 40 Jawhar M, "MARS : mutationadjusted risk score for advanced systemic mastocytosis" 37 : 2846-, 2019
• 41 Barete S, "Long-term efficacy and safety of cladribine(2-CdA)in adult patients with mastocytosis" 126 : 1009-1016, 2015
• 42 Arock M, "KIT mutation analysis in mast cell neoplasms : recommendations of the European Competence Network on Mastocytosis" 29 : 1223-1232, 2015
• 43 Sperr WR, "International prognostic scoring system for mastocytosis(IPSM) : a retrospective cohort study" 6 : e638-49, 2019
• 44 Arber DA, "International Consensus Classification of Myeloid Neoplasms and Acute Leukemias : integrating morphologic, clinical, and genomic data" 140 : 1200-1228, 2022
• 45 Simon J, "Interest of interferon alpha in systemic mastocytosis. The French experience and review of the literature" 52 : 294-299, 2004
• 46 Valent P, "Induction of differentiation of human mast cells from bone marrow and peripheral blood mononuclear cells by recombinant human stem cell factor/kit-ligand in long-term culture" 80 : 2237-2245, 1992
• 47 Muñoz-González JI, "Impact of somatic and germline mutations on the outcome of systemic mastocytosis" 2 : 2814-2828, 2018
• 48 Galli SJ, "Immunomodulatory mast cells : negative, as well as positive, regulators of immunity" 8 : 478-486, 2008
• 49 Nagata H, "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" 92 : 10560-10564, 1995
• 50 Valent P, "How I treat patients with advanced systemic mastocytosis" 116 : 5812-5817, 2010
• 51 Ustun C, "Hematopoietic stem-cell transplantation for advanced systemic mastocytosis" 32 : 3264-, 2014
• 52 Cherner JA, "Gastrointestinal dysfunction in systemic mastocytosis : a prospective study" 95 : 657-667, 1988
• 53 Muñoz-González JI, "Frequency and prognostic impact of KIT and other genetic variants in indolent systemic mastocytosis" 134 : 456-468, 2019
• 54 Reiter A, "Efficacy of avapritinib versus best available therapy in the treatment of advanced systemic mastocytosis" 36 : 2108-2120, 2022
• 55 Gotlib J, "Efficacy and safety of midostaurin in advanced systemic mastocytosis" 374 : 2530-2541, 2016
• 56 Reiter A, "Efficacy and safety of avapritinib in previously treated patients with advanced systemic mastocytosis" 6 : 5750-5762, 2022
• 57 Gotlib J, "Efficacy and safety of avapritinib in advanced systemic mastocytosis : interim analysis of the phase 2 PATHFINDER trial" 27 : 2192-2199, 2021
• 58 Deininger MW, "Effective control of advance systemic mastocytosis with avapritinib : mutational analysis from the explorer clinical study" 138 (138): 318-, 2021
• 59 Schwartz LB, "Diagnostic value of tryptase in anaphylaxis and mastocytosis" 26 : 451-463, 2006
• 60 Valent P, "Diagnosis and management of mastocytosis : an emerging challenge in applied hematology" 2015 : 98-105, 2015
• 61 Siebenhaar F, "Development and validation of the mastocytosis quality of life questionnaire : MC-QoL" 71 : 869-877, 2016
• 62 Kirshenbaum AS, "Demonstration that human mast cells arise from a progenitor cell population that is CD34(+), c-kit(+), and expresses aminopeptidase N(CD13)" 94 : 2333-2342, 1999
• 63 Valent P, "Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes : a consensus proposal" 157 : 215-225, 2012
• 64 Lim KH, "Cytoreductive therapy in 108 adults with systemic mastocytosis : outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine" 84 : 790-794, 2009
• 65 Ustun C, "Consensus opinion on allogeneic hematopoietic cell transplantation in advanced systemic mastocytosis" 22 : 1348-1356, 2016
• 66 Schwaab J, "Comprehensive mutational profiling in advanced systemic mastocytosis" 122 : 2460-2466, 2013
• 67 Álvarez-Twose I, "Complete response after imatinib mesylate therapy in a patient with well-differentiated systemic mastocytosis" 30 : e126-9, 2012
• 68 Bonadonna P, "Clonal mast cell disorders in patients with systemic reactions to Hymenoptera stings and increased serum tryptase levels" 123 : 680-686, 2009
• 69 Trizuljak J, "Clinical features and survival of patients with indolent systemic mastocytosis defined by the updated WHO classification" 75 : 1927-1938, 2020
• 70 Laroche M, "Clinical and densitometric efficacy of the association of interferon alpha and pamidronate in the treatment of osteoporosis in patients with systemic mastocytosis" 26 : 242-243, 2007
• 71 Kluin-Nelemans HC, "Cladribine therapy for systemic mastocytosis" 102 : 4270-4276, 2003
• 72 Galli SJ, "Basophils and mast cells : morphologic insights into their biology, secretory patterns, and function" 34 : 1-141, 1984
• 73 Jones RL, "Avapritinib in unresectable or metastatic PDGFRA D842V-mutant gastrointestinal stromal tumours : long-term efficacy and safety data from the NAVIGATOR phase I trial" 145 : 132-142, 2021
• 74 Wagner AJ, "Association of combination of conformation-specific KIT inhibitors with clinical benefit in patients with refractory gastrointestinal stromal tumors : a phase 1b/2a nonrandomized clinical trial" 7 : 1343-1350, 2021
• 75 Valent P, "Aggressive systemic mastocytosis and related mast cell disorders : current treatment options and proposed response criteria" 27 : 635-641, 2003
• 76 Carter MC, "Adverse reactions to drugs and biologics in patients with clonal mast cell disorders : a work group report of the Mast Cells Disorder Committee, American Academy of Allergy, Asthma & Immunology" 143 : 880-893, 2019
• 77 Robyn J, "Advances in immunology" Academic Press 169-243, 2006
• 78 Jawhar M, "Additional mutations in SRSF2, ASXL1 and/or RUNX1 identify a high-risk group of patients with KIT D816V+ advanced systemic mastocytosis" 30 : 136-143, 2016
• 79 Gotlib J, "Activity of the tyrosine kinase inhibitor PKC412 in a patient with mast cell leukemia with the D816V KIT mutation" 106 : 2865-2870, 2005
• 80 Dave N, "Abstract CT122: safety and pharmacokinetics of BLU-263, a next-generation KIT inhibitor, in normal healthy volunteers" 81 (81): CT122-, 2021
• 81 Buchdunger E, "Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors" 295 : 139-145, 2000
• 82 DeAngelo DJ, "AZURE : a phase 1/2 study of blu-263 as monotherapy and in combination with azacitidine in patients with advanced systemic mastocytosis" 140 (140): 6877-6878, 2022
• 83 Evans EK, "A precision therapy against cancers driven by KIT/PDGFRA mutations" 9 : eaao1690-, 2017
• 84 Castells M, "A phase 2/3 study of BLU-263 in patients with indolent systemic mastocytosis or monoclonal mast cell activation syndrome" 149 : AB221-, 2022
• 85 Gotlib J, "A phase 2 study of bezuclastinib(CGT9486), an oral, selective, and potent KIT D816V inhibitor, in adult patients with advanced systemic mastocytosis(AdvSM)" 138 (138): 3636-, 2021
• 86 Akin C, "A novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib" 103 : 3222-3225, 2004
• 87 Carter MC, "A distinct biomolecular profile identifies monoclonal mast cell disorders in patients with idiopathic anaphylaxis" 141 : 180-188, 2018