Identification of the Ki-1 antigen (CD30) as a novel therapeutic target in systemic mastocytosis

Blatt, Katharina; Cerny-Reiterer, Sabine; Schwaab, Juliana; Sotlar, Karl; Eisenwort, Gregor; Stefanzl, Gabriele; Hoermann, Gregor; Mayerhofer, Matthias; Schneeweiss, Mathias; Knapp, Sylvia; Rülicke, Thomas; Hadzijusufovic, Emir; Bauer, Karin; Smiljkovic, Dubravka; Willmann, Michael; Reiter, Andreas; Horny, Hans‐Peter; Valent, Peter

doi:10.1182/blood-2015-03-637728

Cited by 49 publications

(56 citation statements)

References 54 publications

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“…In initial investigations, CD30 was found to be primarily expressed in MCs in advanced SM (62). However, although a correlation does exist, CD30 is not an absolute marker of advanced SM (ASM, MCL, SM-AHN), but is also detectable in MCs in many patients with ISM (59,63). CD30 may thus not be an optimal grading-marker in SM, but may qualify as a new minor criterion of SM, similar to CD25.…”

Section: Most Recent Advances In the Classification And Criteria Defimentioning

confidence: 98%

“…Such MCL-initiating stem cells have recently been identified in advanced SM (98). One effective approach to kill such quiescent (stem) cells may be to apply antibody-based toxin conjugates or other targeted antibodies (63,99,100). The CD30 antibody-based drug brentuximab-vedotin has recently been considered for the treatment of patients with advanced SM (63) and a clinical trial in patients with CD30+ ASM and MCL has recently been initiated in the USA.…”

Section: New Treatment Options For Patients With Advanced Smmentioning

confidence: 99%

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Advances in the Classification and Treatment of Mastocytosis: Current Status and Outlook toward the Future

et al. 2017

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Mastocytosis is a term used to denote a heterogeneous group of conditions defined by expansion and accumulation of clonal (neoplastic) tissue mast cells in various organs. The classification of the World Health Organization (WHO) divides the disease into cutaneous mastocytosis (CM), systemic mastocytosis (SM), and localized mast cell tumors. Based on histomorphologic criteria, clinical parameters, and organ involvement, SM is further divided into indolent SM (ISM) and advanced SM variants, including aggressive SM (ASM) and mast cell leukemia (MCL). The clinical impact and prognostic value of this classification has been confirmed in numerous studies, and its basic concept remains valid. However, refinements have recently been proposed by the consensus group, the WHO, and the European Competence Network on Mastocytosis (ECNM). In addition, new treatment options are available for patients with advanced SM, including allogeneic hematopoietic stem cell transplantation and multi-kinase inhibitors directed against KIT D816V and other key signalling molecules. Our current article provides an overview of recent advances in the field of mastocytosis, with emphasis on classification, prognostication, and emerging new treatment options in advanced SM.

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Section: Most Recent Advances In the Classification And Criteria Defimentioning

confidence: 98%

Section: New Treatment Options For Patients With Advanced Smmentioning

confidence: 99%

Advances in the Classification and Treatment of Mastocytosis: Current Status and Outlook toward the Future

et al. 2017

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“…[65][66][67][68][69][70][71] Antibody-based drugs directed against these targets may induce cell lysis or apoptosis in neoplastic MCs. 66,69,70 In addition, initial clinical observations suggest that antibody-based drugs exert antineoplastic effects in patients with advanced SM. 72,73 A summary of surface markers and potential targets expressed by neoplastic MCs is shown in Figure 1 and supplemental Table 5.…”

Section: Epigenetic Targets and Survival-related Moleculesmentioning

confidence: 99%

Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts

Valent

Akin

Metcalfe

2017

Blood

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Over the past few years, substantial advances have been made in understanding the pathogenesis, evolution, and complexity of mast cell neoplasms. New diagnostic and prognostic parameters and novel therapeutic targets with demonstrable clinical impact have been identified. Several of these new markers, molecular targets, and therapeutic approaches have been validated and translated into clinical practice. At the same time, the classification of mastocytosis and related diagnostic criteria have been refined and updated by the consensus group and the World Health Organization (WHO). As a result, more specific therapies tailored toward prognostic subgroups of patients have been developed. Emerging treatment concepts use drugs directed against KIT and other relevant targets in neoplastic mast cells and will hopefully receive recognition by health authorities in the near future. This article provides an overview of recent developments in the field, with emphasis on the updated WHO classification, refined criteria, additional prognostic parameters, and novel therapeutic approaches. Based on these emerging concepts, the prognosis, quality of life, and survival of patients with advanced mastocytosis are expected to improve in the coming years.

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“…CD30 has been targeted with some success for relapsed hematological malignancies. CD30 can be expressed on the cell surface and in the cytoplasm but correlation between surface expression of CD30 and expression of cytoplasmic CD30 remains unclear (Blatt et al, 2015). CD30 targeting has shown to produce growth inhibition (G2/M cell cycle arrest) and apoptosis in neoplastic cells.…”

Section: Discussionmentioning

confidence: 99%

Brentuximab vedotin for treatment of non-Hodgkin lymphomas: A systematic review

Berger

McBride

Lawson

et al. 2017

Critical Reviews in Oncology/Hematology

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Background Brentuximab vedotin (BV) is an antibody-drug conjucate (ADC) comprising a CD30-directed antibody, conjugated to the microtubule-disrupting agent MMAE via a protease cleavable linker. BV is FDA approved for use in relapsed classical Hodgkin lymphoma (HL) and relapsed systemic anaplastic large cell lymphoma (sALCL). There are multiple publications for its utility in other malignancies such as diffuse large B-cell lymphoma (DLBCL), mycosis fungoides (MF), Sézary syndrome (SS), T-cell lymphomas (TCL), primary mediastinal lymphoma (PMBL), and post-transplant lymphoproliferative disorders (PTLD). We believe that BV could potentially provide a strong additional treatment option for patients suffering from NHL. Objective Perform a systematic review on the use of BV in non-Hodgkin lymphoma (NHL) and other CD30+ malignancies in humans. Data sources We searched various databases including PubMed (1946–2015), EMBASE (1947–2015), and Cochrane Central Register of Controlled Trials (1898–2015). Eligibility criteria Inclusion criteria specified all studies and case reports of NHLs in which BV therapy was administered. Included studies A total of 28 articles met these criteria and are summarized in this manuscript. Conclusion Our findings indicate that BV induces a variety of responses, largely positive in nature and variable between NHL subtypes. With additional, properly powered prospective studies, BV may prove to be a strong candidate in the treatment of various CD30+ malignancies.

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Identification of the Ki-1 antigen (CD30) as a novel therapeutic target in systemic mastocytosis

Cited by 49 publications

References 54 publications

Advances in the Classification and Treatment of Mastocytosis: Current Status and Outlook toward the Future

Advances in the Classification and Treatment of Mastocytosis: Current Status and Outlook toward the Future

Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts

Brentuximab vedotin for treatment of non-Hodgkin lymphomas: A systematic review

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