Treatment of CD30-positive systemic mastocytosis with brentuximab vedotin

Borate, Uma; Mehta, Amitkumar; Reddy, Vishnu; Tsai, Michaela Long; Josephson, Neil C.; Schnadig, Ian D.

doi:10.1016/j.leukres.2016.02.010

Cited by 39 publications

(24 citation statements)

References 38 publications

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“…Recent data suggest that CD30 is expressed in human neoplastic MC and serves as a molecular target in advanced SM . Preliminary data from a small case series in human CD30‐positive mastocytosis support this hypothesis although not all patients may respond to brentuximab . In this study, we show that CD30 is also expressed in neoplastic canine MC independent of the histopathological grade.…”

Section: Discussionsupporting

confidence: 70%

IL‐4 downregulates expression of the target receptor CD30 in neoplastic canine mast cells

Bauer

Hadzijusufovic

Cerny-Reiterer

et al. 2016

Vet Comparative Oncology

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CD30 is a novel therapeutic target in human mast cell (MC) neoplasms. In this 'comparative oncology' study, we examined CD30 expression and regulation in neoplastic canine MC using a panel of immunomodulatory cytokines [interleukin-2 (IL-2), IL-4, IL-5, IL-6, IL-13 and stem cell factor (SCF)] and the canine mastocytoma cell lines NI-1 and C2. Of all cytokines tested IL-4 was found to downregulate expression of CD30 in NI-1 and C2 cells. We also found that the CD30-targeting antibody-conjugate brentuximab vedotin induces growth inhibition and apoptosis in both MC lines. Next, we asked whether IL-4-induced downregulation of CD30 interferes with brentuximab vedotin-effects. Indeed, pre-incubation of NI-1 cells with IL-4 decreased responsiveness towards brentuximab vedotin. To overcome IL-4-mediated resistance, we applied drug combinations and found that brentuximab vedotin synergizes with the Kit-targeting drugs masitinib and PKC412 in inhibiting growth of NI-1 and C2 cells. In summary, CD30 is a new marker and IL-4-regulated target in neoplastic canine MC.

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Section: Discussionsupporting

confidence: 70%

IL‐4 downregulates expression of the target receptor CD30 in neoplastic canine mast cells

Bauer

Hadzijusufovic

Cerny-Reiterer

et al. 2016

Vet Comparative Oncology

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“…Given the reported aberrant expression of CD30 on neoplastic MC, with preferential expression in advanced SM as compared to ISM (see above) , the role of brentuximab vedotin in treating advanced SM including MCL is being currently studied (http://Clinicaltrials.gov study# NCT01807598). In a preliminary report, two of four SM patients treated with brentuximab had a response .…”

Section: Treatmentmentioning

confidence: 95%

Systemic mastocytosis in adults: 2017 update on diagnosis, risk stratification and management

Pardanani

2016

American J Hematol

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Disease overview:Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in one or more extra‐cutaneous organs. Diagnosis: The major criterion is presence of multifocal clusters of morphologically abnormal MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC expression of CD25 and/or CD2, and presence of KITD816V. Risk stratification: The 2008 World Health Organization (WHO) classification of SM has been shown to be prognostically relevant. Classification of SM patients into indolent (SM), aggressive SM (ASM), SM associated with a clonal non‐MC lineage disease (SM‐AHNMD) and mast cell leukemia (MCL) subgroups is a useful first step in establishing prognosis. Management: SM treatment is generally palliative. ISM patients have a normal life expectancy and receive symptom‐directed therapy; infrequently, cytoreductive therapy may be indicated for refractory symptoms. ASM patients have disease‐related organ dysfunction; interferon‐α (±corticosteroids) can control dermatological, hematological, gastrointestinal, skeletal and mediator‐release symptoms, but is hampered by poor tolerability. Similarly, cladribine has broad therapeutic activity, with particular utility when rapid MC debulking is indicated; the main toxicity is myelosuppression. Imatinib has a therapeutic role in the presence of an imatinib‐sensitive KIT mutation or in KITD816‐unmutated patients. Treatment of SM‐AHNMD is governed primarily by the non‐MC neoplasm; hydroxyurea has modest utility in this setting; there is a role for allogeneic stem cell transplantation in select cases. Investigational drugs: Recent data confirms midostaurin's significant anti‐MC activity in patients with advanced SM. Am. J. Hematol. 91:1147–1159, 2016. © 2016 Wiley Periodicals, Inc.

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“…Although the authors of a little case series reported some durable response [35], the role of brentuximab-vedotin in the treatment of SM is still being debated.…”

Section: New Drugsmentioning

confidence: 99%

Mastocytosis: One Word for Different Diseases

et al. 2018

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Mastocytosis is a neoplastic disease originating from tissue infiltration by transformed mast cells. The diagnosis requires a high grade of suspicion due to the large variety of presenting symptoms. The World Health Organization classification recognizes localized (cutaneous) and systemic forms of the disease, with these forms showing different degrees of aggressiveness. Mastocytosis is often a multiorgan disease, and its correct management requires a multidisciplinary team of experienced consultants to provide overall patient care. Bone marrow evaluation by molecular analyses, skeleton X-ray and abdominal scan together with allergologic and dermatologic evaluation constitute the essential diagnostic work-up for adult patients with mastocytosis. As clinical situations vary, treatment options range from the use of drugs to treat the symptoms, such as anti-H1 receptors and steroids, to UV irradiation, which is overwhelmingly used in patients with cutaneous mastocytosis (CM) or indolent systemic mastocytosis, to cytoreductive treatment to control life-threatening symptoms or organ damage in the more aggressive forms of the disease. Prognosis also widely differs among patients diagnosed with mastocytosis, with the spectrum ranging from an almost normal life expectancy for those with CM and to less than 1-year median overall survival for those with mast cell leukemia.

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Treatment of CD30-positive systemic mastocytosis with brentuximab vedotin

Cited by 39 publications

References 38 publications

IL‐4 downregulates expression of the target receptor CD30 in neoplastic canine mast cells

IL‐4 downregulates expression of the target receptor CD30 in neoplastic canine mast cells

Systemic mastocytosis in adults: 2017 update on diagnosis, risk stratification and management

Mastocytosis: One Word for Different Diseases

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