Endokrinologische Nebenwirkungen einer onkologischen Therapie mit Anti-CTLA-4-Antikörpern

 

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Zusammenfassung

Neue immunmodulierende Therapien wie monoklonale Anti-CTLA-4-Antikörper werden zunehmend als onkologische Therapien eingesetzt. Gut untersucht und dokumentiert ist Ipilimumab, zur Behandlung des metastasierten Melanoms, das jedoch auch bei anderen soliden Tumoren untersucht wird.

Durch Blockade der auf Lymphozyten lokalisierten CTLA-4-Rezeptoren soll die tumorvermittelte Immuntoleranz, die zur ungehemmten Proliferation von Tumorzellen beiträgt, blockiert werden. Damit verbunden ist eine T-Zellaktivierung die ein Spektrum von Nebenwirkungen hervorruft, die als sog. „immun-related adverse events“ (IRAE) bezeichnet werden. IRAE betreffen auch das endokrine System und führen zu Hypophysitis, Thyreoiditis oder Adrenalitis. Häufig präsentieren sich davon betroffene Patienten mit rel. unspezifischen Symptomen. Insbesondere die unbemerkte und unbehandelte Nebennierenrinden-Insuffizienz kann fatale Folgen haben. Ausgehend von einem Fallbeispiel und der aktuellen Literatur zeigt der folgende Artikel das Spektrum, sowie die zielgerichtete Diagnostik und Therapie von IRAEs unter Ipilimumab.

Abstract

New immune-modulating treatments like the anti-CTLA-4-antibodies-based therapies are increasingly used in medical oncology. The action of Ipilimumab, a monoclonal anti-CTLA-4-antibody used for the treatment of metastasized melanoma and other solid tumors, is well documented. Blocking the CTLA-4-receptors on lymphocytes leads to T-cell acitivation and hence reduction of the tumor-mediated immuntolerance. This mechanism constitutes the basis of the antiproliferative effects but is also responsible for a spectrum of specific adverse events (immune-related adverse events, IRAE). IRAE of the endocrine system comprise hypophysitis, thyroiditis and adrenalitis. Especially adrenal insufficiency can be fatal when not diagnosed and treated. Symptoms often are unspecific and early diagnosis and targeted treatment are crucial. We present a case report and summarize – based upon the current literature – the diagnosis and treatment of endocrinologic IRAEs.

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