title: Treatment of CD30-positive systemic mastocytosis with brentuximab vedotin.
abstract: Systemic mastocytosis is a myeloproliferative neoplasm with varying presentation that is caused by infiltration of neoplastic mast cells into extracutaneous tissues. Cytoreductive therapy is used to control organ dysfunction in aggressive systemic mastocytosis and is sometimes needed for control of severe refractory symptoms in patients with indolent disease. However, current standard cytoreductive agents are limited by their suboptimal degree and duration of response and associated significant toxicities, highlighting the need for novel treatments for systemic mastocytosis. Recent studies have identified CD30 as a therapeutic target in systemic mastocytosis, as CD30 is expressed on a majority of neoplastic mast cells. In this case series, the clinical outcomes of 4 patients with aggressive or indolent systemic mastocytosis treated with the anti-CD30 antibody-drug conjugate brentuximab vedotin are reported. Two patients showed evidence of a response to treatment with a reduction in disease burden, 1 of which has demonstrated a durable response with ongoing benefit for more than 3 years. Treatment with brentuximab vedotin was well-tolerated with side effects that were effectively managed by dose modifications. The results presented suggest that brentuximab vedotin is active in systemic mastocytosis and can induce durable responses with a manageable toxicity profile.
authors.affiliation: Oregon Health & Science University, Mail Code L586, Division of Hematology and Medical Oncology, 3181 SW Sam Jackson Park Road, Portland, OR 97239 USA. Electronic address: borate@ohsu.edu.
authors.forename: Uma
authors.initials: U
authors.lastname: Borate
authors.affiliation: University of Alabama at Birmingham, Department of Medicine, Division of Hematology and Oncology, 1720 2nd Avenue South, NP2540, Birmingham, AL 35294, USA.
authors.forename: Amitkumar
authors.initials: A
authors.lastname: Mehta
authors.affiliation: University of Alabama at Birmingham, Department of Pathology, Division of Laboratory Medicine, 619 19th Street South, WP, P230A, Birmingham, AL 35249, USA.
authors.forename: Vishnu
authors.initials: V
authors.lastname: Reddy
authors.affiliation: Minneapolis Clinic, 910 E 26th Street, Suite 200, Minneapolis, MN 55404, USA.
authors.forename: Michaela
authors.initials: M
authors.lastname: Tsai
authors.affiliation: Seattle Genetics, Inc., 21823 30th Drive SE, Bothell, WA 98021, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Josephson
authors.affiliation: Compass Oncology, US Oncology Research 19260 SW 65th Avenue, Suite 435, Tualatin, OR 97062, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Schnadig
mesh_terms: D000328:Adult; D000368:Aged; D000079963:Brentuximab Vedotin; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D007124:Immunoenzyme Techniques; D017730:Ki-1 Antigen / Q000378:metabolism*; D008297:Male; D034721:Mastocytosis, Systemic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis
chemical_list: D018796:Immunoconjugates; D017730:Ki-1 Antigen; D000079963:Brentuximab Vedotin
keywords: Brentuximab vedotin; Clinical trial; Hematologic neoplasms; Immunoconjugates; Mast cells; Monomethyl auristatin E