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      Stadium III Melanom: Können immunologische Nebenwirkungen ein gutes Zeichen sein?

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      Karger Kompass Onkologie

      S. Karger AG

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          Abstract

          Alexander Eggermont und Mitarbeiter haben die EORTC 1325/KEYNOTE-054 Studie [<xref ref-type="bibr" rid="ref1">1</xref>] als Ausgangspunkt für weitere Untersuchungen gewählt. Sie gingen der Frage nach, ob das tumorfreie Überleben (relaps-free survival, RFS) bei Stadium III Melanom Patienten vom Auftreten immunologisch vermittelter unerwünschter Nebenwirkungen (immun-related adverse events, irAE) beeinflusst wird. Die EORTC 1325/KEYNOT-054 Studie vergleicht die Therapie mit dem Immuncheckpoint-Inhibitor (ICI) Pembrolizumab (Pem) zu Placebo. Eingeschlossen wurden nicht vorbehandelte Patienten im Stadium III (AJCC 2009) ohne bekannte Autoimmunerkrankungen, die mindestens eine Mikrometastase von 1mm Durchmesser im Sentinel-Lymphknoten hatten, eine komplettierende regionäre Lymphadenektomie erhalten hatten und bei Studieneinschluss tumorfrei waren. Pembrolizumab (200mg) wurde i.v. alle 3 Wochen für maximal 18 Gaben verabreicht. Von 1011 Patienten begannen 509 mit Pem und 505 mit Placebo , wobei Alter, Body-Mass-Index, Tumorstadien (IIIA, IIIB und IIIC), BRAF-Mutationsstatus und PD-L1 Expression in den Gruppen ohne signifikante Unterschiede waren [<xref ref-type="bibr" rid="ref1">1</xref>]. Die irAE wurden in 3 Gruppen eingeteilt: 1.) endokrine AE (Hypo- oder Hyperthyreoidismus, Thyreoiditis, Hypophysitis, Diabetes mellitus Typ I, Niereninsuffizienz), 2.) Vitiligo und 3.) alle irAE (endokrine AE, Pneumonitis/interstitielle Lungenerkrankung, Sarcoidose, Vitiligo, schwere Hautreaktionen, Kolitis, Pankreatitis, Hepatitis, Nephritis, Uveitis, Myositis oder Myocarditis). Verschiedene statistische Rechenmodelle (z.B. Cox Regressionsmethode mit ergänzenden zeitvariablen Indikatoren) wurden zur Abschätzung der Assoziation vom Auftreten von irAE und RFS bei Patienten im Pem- und Placebo-Arm sowie zur Betrachtung des Einflusses einer systemischen Steroidgabe auf die Zielvariablen verwendet.

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          Is Open Access

          Significant association between tumor mutational burden and immune-related adverse events during immune checkpoint inhibition therapies

          More than 2000 immuno-oncology agents are being tested or are in use as a result of the cancer immunotherapy revolution. Manipulation of co-inhibitory receptors has achieved tumor eradication in a minority of patients, but widespread immune-related adverse events (irAEs) compromised tolerance to healthy self-tissues in the majority. We have proposed that a major mechanism of irAEs is similar to a graft-versus-malignancy effect of graft-versus-host disease. To verify our hypothesis, we retrieved post-marketing data of adverse events from the U.S. Food and Drug Administration Adverse Event Reporting System. A significant positive correlation was revealed in 7677 patients between the reporting odds ratio of irAEs during immune checkpoint inhibitor therapy and the corresponding tumor mutational burden across 19 cancer types. These results can be interpreted to mean that the ICI drugs unleashed T cells against “altered-self,” self, and tumors resulting in better overall survival. Electronic supplementary material The online version of this article (10.1007/s00262-020-02543-6) contains supplementary material, which is available to authorized users.
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            The Great Debate at "Melanoma Bridge", Naples, December 7th, 2019

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              Moving towards personalized treatments of immune-related adverse events

               K Esfahani (2021)
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                Author and article information

                Journal
                KKO
                10.1159/issn.2296-5416
                Karger Kompass Onkologie
                S. Karger AG
                2296-5416
                2296-5386
                2020
                September 2020
                27 August 2020
                : 7
                : 3
                : 138-139
                Affiliations
                Facharzt für Dermatologie und Venerologie, medikamentöse Tumortherapie, Allergologie, Proktologie und Phlebologie, Köln, Deutschland
                Author notes
                *Dr. Jan Maschke, Facharzt für Dermatologie und Venerologie, medikamentöse Tumortherapie, Allergologie, Proktologie und Phlebologie, Hauptstrasse 89, 50996 Köln, Deutschland, dermatologie-drmaschke@gmx.de
                Article
                510160 Kompass Onkol 2020;7:138–139
                10.1159/000510160
                © 2020 S. Karger GmbH, Freiburg

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Pages: 2
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/510160
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