{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T23:47:11Z","timestamp":1778197631408,"version":"3.51.4"},"reference-count":45,"publisher":"American Society of Hematology","issue":"15","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,8,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>There is an unmet need for effective therapies for advanced systemic mastocytosis (advSM). CD30 is expressed on the surface of neoplastic mast cells (MC) in more than 50% of patients with advSM. Brentuximab vedotin (BV) is a CD30-directed antibody-drug conjugate with preclinical evidence supporting both an antineoplastic effect and an attenuation of immunoglobulin E-associated mediator release. These observations are the basis for this phase 2 trial of BV monotherapy (1.8 mg\/kg IV every 3 weeks up to 8 cycles) in patients with CD30-positive advSM. The primary objective was to determine the efficacy of BV according to International Working Group-Myeloproliferative Neoplasms Research and Treatment-European Competence Network on Mastocytosis (IWG-MRT-ECNM) response criteria. Secondary objectives included evaluation of safety, changes in bone marrow (BM) MC burden, serum tryptase level, flow cytometric quantification of MC surface expression of CD30, and self-reported symptom burden. The trial enrolled 10 patients with a diagnosis of CD30+ advSM (aggressive SM, SM with an associated hematologic neoplasm [SM-AHN], or mast cell leukemia [MCL]) with 1 or more signs of SM-related organ damage. According to IWG-MRT-ECNM criteria, none of the patients demonstrated better than stable disease with BV. In addition, there were no significant reductions in BM MC burden, serum tryptase levels, or MC surface expression of CD30. Self-reported symptom scores showed no durable improvement with BV treatment. We conclude that BV is not active as a single agent in CD30+ advSM. This trial was registered at www.clinicaltrials.gov as #NCT01807598.<\/jats:p>","DOI":"10.1182\/bloodadvances.2019000152","type":"journal-article","created":{"date-parts":[[2019,7,26]],"date-time":"2019-07-26T16:55:13Z","timestamp":1564160113000},"page":"2264-2271","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":18,"title":["A phase 2 study of brentuximab vedotin in patients with CD30-positive advanced systemic mastocytosis"],"prefix":"10.1182","volume":"3","author":[{"given":"Jason","family":"Gotlib","sequence":"first","affiliation":[{"name":"Division of Hematology, Stanford Cancer Institute, Stanford, CA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8291-6546","authenticated-orcid":false,"given":"John H.","family":"Baird","sequence":"additional","affiliation":[{"name":"Division of Hematology, Stanford Cancer Institute, Stanford, CA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5478-7847","authenticated-orcid":false,"given":"Tracy I.","family":"George","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of New Mexico, Albuquerque, NM; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheryl","family":"Langford","sequence":"additional","affiliation":[{"name":"Division of Hematology, Stanford Cancer Institute, Stanford, CA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Reyes","sequence":"additional","affiliation":[{"name":"Division of Hematology, Stanford Cancer Institute, Stanford, CA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin","family":"Abuel","sequence":"additional","affiliation":[{"name":"Division of Hematology, Stanford Cancer Institute, Stanford, CA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecelia","family":"Perkins","sequence":"additional","affiliation":[{"name":"Division of Hematology, Stanford Cancer Institute, Stanford, CA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kurt","family":"Schroeder","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prithviraj","family":"Bose","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srdan","family":"Verstovsek","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","published-online":{"date-parts":[[2019,7,26]]},"reference":[{"issue":"6","key":"2020021108181192200_B1","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1038\/leu.2015.24","article-title":"KIT mutation analysis in mast cell neoplasms: recommendations of the European Competence Network on Mastocytosis","volume":"29","author":"Arock","year":"2015","journal-title":"Leukemia"},{"issue":"2","key":"2020021108181192200_B2","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1046\/j.1365-2141.2001.02783.x","article-title":"Mutation analysis of C-KIT in patients with myelodysplastic syndromes without mastocytosis and cases of systemic mastocytosis","volume":"113","author":"Fritsche-Polanz","year":"2001","journal-title":"Br J Haematol"},{"issue":"7","key":"2020021108181192200_B3","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1182\/blood-2006-04-015545","article-title":"KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients","volume":"108","author":"Garcia-Montero","year":"2006","journal-title":"Blood"},{"issue":"9","key":"2020021108181192200_B4","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1038\/modpathol.2011.84","article-title":"Evaluation of the WHO criteria for the classification of patients with mastocytosis","volume":"24","author":"S\u00e1nchez-Mu\u00f1oz","year":"2011","journal-title":"Mod Pathol"},{"issue":"2","key":"2020021108181192200_B5","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.iac.2014.01.009","article-title":"Molecular defects in mastocytosis: KIT and beyond KIT","volume":"34","author":"Bibi","year":"2014","journal-title":"Immunol Allergy Clin North Am"},{"issue":"24","key":"2020021108181192200_B6","doi-asserted-by":"crossref","first-page":"4846","DOI":"10.1182\/blood-2011-12-397588","article-title":"In aggressive forms of mastocytosis, TET2 loss cooperates with c-KITD816V to transform mast cells","volume":"120","author":"Soucie","year":"2012","journal-title":"Blood"},{"issue":"20","key":"2020021108181192200_B7","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"key":"2020021108181192200_B8","unstructured":"Horny\n              HP\n            , AkinC, ArberDA, et al. Mastocytosis. In: SwerdlowSH, CampoE, HarrisNL, eds., et al. WHO classification of tumors of hematopoietic and lymphoid tissues, 4th ed. Lyon, France: IARC Press; 2017:62."},{"issue":"23","key":"2020021108181192200_B9","doi-asserted-by":"crossref","first-page":"5727","DOI":"10.1182\/blood-2009-02-205237","article-title":"Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors","volume":"113","author":"Lim","year":"2009","journal-title":"Blood"},{"issue":"2","key":"2020021108181192200_B10","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1097\/MOH.0b013e3283366c59","article-title":"Systemic mastocytosis in adults: a review on prognosis and treatment based on 342 Mayo Clinic patients and current literature","volume":"17","author":"Pardanani","year":"2010","journal-title":"Curr Opin Hematol"},{"issue":"3","key":"2020021108181192200_B11","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.jaci.2009.05.003","article-title":"Prognosis in adult indolent systemic mastocytosis: a long-term study of the Spanish Network on Mastocytosis in a series of 145 patients","volume":"124","author":"Escribano","year":"2009","journal-title":"J Allergy Clin Immunol"},{"issue":"1","key":"2020021108181192200_B12","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1182\/blood-2009-10-249979","article-title":"WHO subvariants of indolent mastocytosis: clinical details and prognostic evaluation in 159 consecutive adults","volume":"115","author":"Pardanani","year":"2010","journal-title":"Blood"},{"issue":"18","key":"2020021108181192200_B13","doi-asserted-by":"crossref","first-page":"3769","DOI":"10.1182\/blood-2009-05-220145","article-title":"Prognostically relevant breakdown of 123 patients with systemic mastocytosis associated with other myeloid malignancies","volume":"114","author":"Pardanani","year":"2009","journal-title":"Blood"},{"issue":"8","key":"2020021108181192200_B14","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1182\/blood-2012-07-442400","article-title":"Mast cell leukemia","volume":"121","author":"Georgin-Lavialle","year":"2013","journal-title":"Blood"},{"issue":"12","key":"2020021108181192200_B15","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1002\/ajh.21561","article-title":"Cytoreductive therapy in 108 adults with systemic mastocytosis: Outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine","volume":"84","author":"Lim","year":"2009","journal-title":"Am J Hematol"},{"issue":"8","key":"2020021108181192200_B16","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1182\/blood-2014-12-614743","article-title":"Long-term efficacy and safety of cladribine (2-CdA) in adult patients with mastocytosis","volume":"126","author":"Barete","year":"2015","journal-title":"Blood"},{"issue":"21","key":"2020021108181192200_B17","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.1182\/blood.V116.21.1982.1982","article-title":"Long term efficacy and safety of cladribine in adult systemic mastocytosis: a French multicenter study of 44 patients","volume":"116","author":"Hermine","year":"2010","journal-title":"Blood"},{"issue":"4","key":"2020021108181192200_B18","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1046\/j.1365-2141.2002.03944.x","article-title":"Treatment of adult systemic mastocytosis with interferon-alpha: results of a multicentre phase II trial on 20 patients","volume":"119","author":"Casassus","year":"2002","journal-title":"Br J Haematol"},{"issue":"26","key":"2020021108181192200_B19","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.1056\/NEJMoa1513098","article-title":"Efficacy and safety of midostaurin in advanced systemic mastocytosis","volume":"374","author":"Gotlib","year":"2016","journal-title":"N Engl J Med"},{"issue":"suppl 1","key":"2020021108181192200_B20","first-page":"Abstract 2","article-title":"Clinical activity in a phase 1 study of Blu-285, a potent, highly-selective inhibitor of KIT D816V in advanced systemic mastocytosis (AdvSM) [abstract]","volume":"130","author":"DeAngelo","year":"2017","journal-title":"Blood"},{"issue":"S1","key":"2020021108181192200_B21","first-page":"Abstract PF612","article-title":"Avapritinib (BLU-285), a selective KIT inhibitor, is associated with high response rate and tolerable safety profile in advanced systemic mastocytosis: results of a phase 1 study [abstract]","volume":"2","author":"Deininger","year":"2018","journal-title":"HemaSphere"},{"issue":"2","key":"2020021108181192200_B22","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.iac.2014.01.006","article-title":"CD30 in systemic mastocytosis","volume":"34","author":"van Anrooij","year":"2014","journal-title":"Immunol Allergy Clin North Am"},{"issue":"4","key":"2020021108181192200_B23","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/modpathol.2010.224","article-title":"Aberrant expression of CD30 in neoplastic mast cells in high-grade mastocytosis","volume":"24","author":"Sotlar","year":"2011","journal-title":"Mod Pathol"},{"issue":"6","key":"2020021108181192200_B24","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1111\/his.12221","article-title":"CD30 expression by bone marrow mast cells from different diagnostic variants of systemic mastocytosis","volume":"63","author":"Morgado","year":"2013","journal-title":"Histopathology"},{"issue":"26","key":"2020021108181192200_B25","doi-asserted-by":"crossref","first-page":"2832","DOI":"10.1182\/blood-2015-03-637728","article-title":"Identification of the Ki-1 antigen (CD30) as a novel therapeutic target in systemic mastocytosis","volume":"126","author":"Blatt","year":"2015","journal-title":"Blood"},{"issue":"4","key":"2020021108181192200_B26","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1182\/blood-2003-01-0039","article-title":"cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity","volume":"102","author":"Francisco","year":"2003","journal-title":"Blood"},{"issue":"18","key":"2020021108181192200_B27","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1200\/JCO.2011.38.0402","article-title":"Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study","volume":"30","author":"Pro","year":"2012","journal-title":"J Clin Oncol"},{"issue":"18","key":"2020021108181192200_B28","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1200\/JCO.2011.38.0410","article-title":"Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin\u2019s lymphoma","volume":"30","author":"Younes","year":"2012","journal-title":"J Clin Oncol"},{"issue":"13","key":"2020021108181192200_B29","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1182\/blood-2012-09-458521","article-title":"International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European Competence Network on Mastocytosis (ECNM) consensus response criteria in advanced systemic mastocytosis","volume":"121","author":"Gotlib","year":"2013","journal-title":"Blood"},{"issue":"33","key":"2020021108181192200_B30","doi-asserted-by":"crossref","first-page":"4098","DOI":"10.1200\/JCO.2012.42.3863","article-title":"Myeloproliferative neoplasm (MPN) symptom assessment form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs","volume":"30","author":"Emanuel","year":"2012","journal-title":"J Clin Oncol"},{"issue":"11","key":"2020021108181192200_B31","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1111\/all.12920","article-title":"Patient-reported disease-specific quality-of-life and symptom severity in systemic mastocytosis","volume":"71","author":"van Anrooij","year":"2016","journal-title":"Allergy"},{"key":"2020021108181192200_B32","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.leukres.2016.02.010","article-title":"Treatment of CD30-positive systemic mastocytosis with brentuximab vedotin","volume":"44","author":"Borate","year":"2016","journal-title":"Leuk Res"},{"issue":"1","key":"2020021108181192200_B33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/cyto.b.10072","article-title":"Immunophenotypic analysis of mast cells in mastocytosis: When and how to do it","volume":"58","author":"Escribano","year":"2004","journal-title":"Cytometry B Clin Cytom"},{"issue":"3","key":"2020021108181192200_B34","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.jaci.2009.10.020","article-title":"Mast cells from different molecular and prognostic subtypes of systemic mastocytosis display distinct immunophenotypes","volume":"125","author":"Teodosio","year":"2010","journal-title":"J. Allergy Clin. Immunol"},{"issue":"2","key":"2020021108181192200_B35","doi-asserted-by":"crossref","first-page":"283","DOI":"10.3109\/10428194.2014.974050","article-title":"New frontiers for brentuximab vedotin for lymphomas","volume":"56","author":"Moskowitz","year":"2015","journal-title":"Leuk Lymphoma"},{"key":"2020021108181192200_B36","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.critrevonc.2016.11.009","article-title":"Brentuximab vedotin for treatment of non-Hodgkin lymphomas: A systematic review","volume":"109","author":"Berger","year":"2017","journal-title":"Crit Rev Oncol Hematol"},{"issue":"10094","key":"2020021108181192200_B37","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/S0140-6736(17)31266-7","article-title":"Brentuximab vedotin or physician\u2019s choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial","volume":"390","author":"Prince","year":"2017","journal-title":"Lancet"},{"issue":"9","key":"2020021108181192200_B38","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1182\/blood-2014-09-598763","article-title":"Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed\/refractory DLBCL with variable CD30 expression","volume":"125","author":"Jacobsen","year":"2015","journal-title":"Blood"},{"issue":"4","key":"2020021108181192200_B39","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1111\/vco.12260","article-title":"IL-4 downregulates expression of the target receptor CD30 in neoplastic canine mast cells","volume":"15","author":"Bauer","year":"2017","journal-title":"Vet Comp Oncol"},{"issue":"8","key":"2020021108181192200_B40","doi-asserted-by":"crossref","first-page":"3011","DOI":"10.1182\/blood.V91.8.3011.3011_3011_3016","article-title":"Serum level of the soluble form of the CD30 molecule identifies patients with Hodgkin\u2019s disease at high risk of unfavorable outcome","volume":"91","author":"Nadali","year":"1998","journal-title":"Blood"},{"issue":"5","key":"2020021108181192200_B41","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1111\/j.1600-0609.2006.00725.x","article-title":"Very high levels of soluble CD30 recognize the patients with classical Hodgkin\u2019s lymphoma retaining a very poor prognosis","volume":"77","author":"Visco","year":"2006","journal-title":"Eur J Haematol"},{"issue":"4","key":"2020021108181192200_B42","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1200\/JCO.1998.16.4.1532","article-title":"Clinical implications of serum levels of soluble CD30 in 70 adult anaplastic large-cell lymphoma patients","volume":"16","author":"Zinzani","year":"1998","journal-title":"J Clin Oncol"},{"issue":"5","key":"2020021108181192200_B43","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1111\/bjh.14317","article-title":"Biomarkers for evaluation of treatment response in classical Hodgkin lymphoma: comparison of sGalectin-1, sCD163 and sCD30 with TARC","volume":"175","author":"Plattel","year":"2016","journal-title":"Br J Haematol"},{"issue":"10","key":"2020021108181192200_B44","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.3109\/10428194.2012.666543","article-title":"Persistence of CD30 expression in Hodgkin lymphoma following brentuximab vedotin (SGN-35) treatment failure","volume":"53","author":"Nathwani","year":"2012","journal-title":"Leuk Lymphoma"},{"issue":"6","key":"2020021108181192200_B45","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1158\/1535-7163.MCT-15-0036","article-title":"CD30 Downregulation, MMAE Resistance, and MDR1 Upregulation Are All Associated with Resistance to Brentuximab Vedotin","volume":"14","author":"Chen","year":"2015","journal-title":"Mol Cancer Ther"}],"container-title":["Blood Advances"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/bloodadvances\/article-pdf\/3\/15\/2264\/1632375\/advancesadv2019000152.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/bloodadvances\/article-pdf\/3\/15\/2264\/1632375\/advancesadv2019000152.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T08:25:59Z","timestamp":1581409559000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/bloodadvances\/article\/3\/15\/2264\/260593\/A-phase-2-study-of-brentuximab-vedotin-in-patients"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,26]]},"references-count":45,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2019,8,13]]}},"URL":"https:\/\/doi.org\/10.1182\/bloodadvances.2019000152","relation":{},"ISSN":["2473-9529","2473-9537"],"issn-type":[{"value":"2473-9529","type":"print"},{"value":"2473-9537","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,26]]}}}