Uveitisinduktion durch immunonkologische Therapien, speziell Checkpoint-Inhibitoren

Zusammenfassung

Hintergrund Immun-Checkpoint- und BRAF-/MEK-Inhibitoren (ICI) haben eine zentrale Stellung in der Krebstherapie eingenommen, da sie eine erhebliche Lebensverlängerung bei einer guten Verträglichkeit und Lebensqualität bewirken. Sie sind jedoch mit stoffklassenspezifischen, nicht toxischen immunologischen Nebenwirkungen, darunter auch Entstehung einer Uveitis, behaftet. In dieser Übersicht soll der aktuelle Kenntnisstand zu Wirkprinzip und systemischen und okulären Nebenwirkungen der ICI dargestellt werden.

Methoden Dieser Übersicht liegt eine Literatursuche in PubMed, der Datenbank des National Institute of Health der USA (https://www.ncbi.nlm.nih.gov/pubmed) mit den Stichworten „uveitis“ AND „drug-induced“ AND/OR „immune checkpoint inhibitor“ zugrunde. Alle relevant erscheinenden Publikationen der letzten 5 Jahre wurden zusammen mit den darin zitierten Querverweisen ausgewertet.

Ergebnisse Ein klassenspezifisches Phänomen der sonst gut verträglichen ICI ist ihre Fähigkeit, eine systemische und okuläre Autoimmunität auszulösen. Diese unterscheidet sich von toxischen Nebenwirkungen durch ihre Dosisunabhängigkeit. Okuläre Nebenwirkungen treten bei 3% der Patienten auf, wobei ein Melanom als Grunderkrankung und eine Therapie mit Pembrolizumab das Risiko um ein Mehrfaches erhöhen. Eine frühe Diagnose und systemische Steroidtherapie dieser potenziell lebensbedrohlichen Nebenwirkung erlauben in > 90% die Erhaltung der Sehfunktion und Lebensqualität, ohne die ICI-Therapie abzusetzen.

Schlussfolgerung Das therapeutische Ansprechen von Malignomen auf ICI bezüglich des Überlebens und der Verträglichkeit, insbesondere bei Melanomen, lässt eine zunehmende Anwendung von ICI auch in Therapiekombinationen und damit eine Zunahme der immunologischen Komplikationen im klinischen Alltag erwarten. In Anbetracht einer Mortalität von unbehandelt bis zu 3% infolge immunvermittelter Nebenwirkungen an multiplen Organen ist eine rasche interdisziplinäre Abklärung und rechtzeitige aggressive Behandlung zwingend, führt aber meist auch zu erfreulichen funktionellen Ergebnissen.

Abstract

Background The recently introduced tumor therapies including immune checkpoint and BRAF/MEK inhibitors (ICI) have substantially contributed to survival and quality of life of the affected patients, but are associated with class-specific, non-toxic immune-related side effects including uveitis. This narrative review focusses to summarize the immune-related adverse event profile associated with the use of ICI.

Methods A literature search in PubMed, the publication database of the National Institute of Health in the USA (https://www.ncbi.nlm.nih.gov/pubmed) used the search terms “uveitis” AND “drug-induced” AND/OR “immune checkpoint inhibitor”. All articles published in the last five years and the for the purpose of this review relevant cross references were evaluated.

Results A class-specific phenomenon of ICI and BRAF/MEK inhibitors is their capability to induce systemic and ocular autoimmunity. Ocular side effects are observed in up to 3% of patients and should be differentiated from toxic side effects, since this is not dose-dependent. Melanoma as underlying disease and Pembrolizumab as ICI significantly increase the risk. If timely recognized, systemic treatment with corticosteroids allows to preserve vision without cessation of the tumor treatment in more than 90% of these potentially life-threatening instances.

Conclusion Given their impact onto the survival of cancer and namely melanoma patients, ICI and BRAF/MEK inhibitors are increasingly used alone and in combination, which enhances their inherent risk of developing drug-induced ocular autoimmunity. Favorable functional outcomes are closely linked to early recognition and aggressive treatment of these complications considering the fact that these immune-related adverse events affect multiple organ systems and have an untreated lethality of up to 3%.

Schlüsselwörter

Immun-Checkpoint-Inhibitor - BRAF-/MEK-Inhibitor - Uveitis - Pembrolizumab - nicht toxische Nebenwirkung - medikamentös induzierte Autoimmunerkrankung

Key words

immune checkpoint inhibitor - BRAF/MEK inhibitor - uveitis - anti-PD1/anti-PD-L1 antibody - immune-related adverse event - drug-induced autoimmunity

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