Second-line therapies for steroid-refractory immune-related adverse events in patients treated with immune checkpoint inhibitors.

Autor: Ruf T; Department of Dermatology and Allergology, University Hospital, LMU Munich, Munich, Germany; SERIO registry., Kramer R; Department of Dermatology, University Clinic Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; SERIO registry., Forschner A; Department of Dermatology, Eberhard-Karls-University of Tübingen, Tübingen, Germany., Leiter U; Department of Dermatology, Eberhard-Karls-University of Tübingen, Tübingen, Germany., Meier F; Department of Dermatology, University Hospital Carl Gustav Carus, TU Dresden, Germany., Reinhardt L; Department of Dermatology, University Hospital Carl Gustav Carus, TU Dresden, Germany., Dücker P; Department of Dermatology, Hospital Dortmund, Dortmund, Germany., Ertl C; Department of Dermatology and Allergology, University Hospital, LMU Munich, Munich, Germany; SERIO registry., Tomsitz D; Department of Dermatology and Allergology, University Hospital, LMU Munich, Munich, Germany., Tietze JK; Clinic for Dermatology and Venerology, University Medical Center Rostock, Rostock, Germany., Gutzmer R; Department of Dermatology, Johannes Wesling Medical Center, Ruhr-University Bochum, Minden, Germany., Dabrowski E; Clinic Ludwigshafen, Ludwigshafen, Germany., Zimmer L; Department of Dermatology, Essen University Hospital, West German Cancer Center, University of Duisburg-Essen and the German Cancer Consortium (DKTK), Partner site Essen/Düsseldorf, Germany., Gesierich A; Department of Dermatology, University Hospital Würzburg, Germany., Zierold S; Department of Dermatology and Allergology, University Hospital, LMU Munich, Munich, Germany; SERIO registry., French LE; Department of Dermatology and Allergology, University Hospital, LMU Munich, Munich, Germany; Dr. Philip Frost Department of Dermatology & Cutaneous Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136, USA., Eigentler T; Department of Dermatology, Charité University Medicine Berlin, Berlin, Germany., Amaral T; Department of Dermatology, Eberhard-Karls-University of Tübingen, Tübingen, Germany; Cluster of Excellence iFIT (EXC 2180), Tübingen, Germany., Heinzerling L; Department of Dermatology and Allergology, University Hospital, LMU Munich, Munich, Germany; Department of Dermatology, University Clinic Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; SERIO registry. Electronic address: Lucie.Heinzerling@med.uni-muenchen.de.
Jazyk: angličtina
Zdroj: European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2024 May; Vol. 203, pp. 114028. Date of Electronic Publication: 2024 Mar 27.
DOI: 10.1016/j.ejca.2024.114028
Abstrakt: Background: Immune checkpoint inhibitors (ICI) induce adverse events (irAEs) that do not respond to steroids, i.e. steroid-refractory (sr) irAEs, and irAEs in which steroids cannot be tapered, i.e. steroid-dependent (sd) irAEs, in about 10% of cases. An evidence-based analysis of the effectiveness of second-line immunosuppressive agents with regard to irAE and tumor control is lacking.
Methods: The international web-based Side Effect Registry Immuno-Oncology (SERIO; http://serio-registry.org) is a collaborative initiative with the Paul-Ehrlich-Institute to document rare, severe, complex or therapy-refractory immunotherapy-induced side effects. The registry was queried on August 1, 2023 for cases of irAEs which were treated with second-line therapies.
Results: From a total of 1330 cases, 217 patients (16.3%) received 249 second-line therapies. A total of 19 different second-line therapies were employed, including TNF-alpha antagonists (46.5%), intravenous immunoglobulins (IVIG; 19.1%), mycophenolate mofetil (15.9%), and methotrexate (3.6%). Therapy choices were determined by the type of irAE. The time to onset of sr-/sd-irAEs after ICI initiation did not consistently differ from steroid-responsive irAEs. While 74.3% of sr-/sd-irAEs resolved and 13.1% had improved, 4.3% persisted, 3.9% resulted in permanent sequelae, and 4.3% in death with ongoing symptoms. Infliximab exhibited potential for earlier symptom improvement compared to mycophenolate mofetil or IVIG. Tumor response in patients with second-line treated sd-/sr-irAE was similar to patients with irAEs treated with steroids only.
Conclusion: Several second-line therapies are effective against sr-/sd-irAEs, the second-line therapies show no clear negative impact on tumor response, and infliximab shows potential for faster improvement of symptoms. However, prospective comparative data are needed.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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