Second-line therapies for steroid-refractory immune-related adverse events in patients treated with immune checkpoint inhibitors
Ruf T, Kramer R, Forschner A, Leiter U, Meier F, Reinhardt L, Dücker P, Ertl C, Tomsitz D, Tietze JK, Gutzmer R, Dabrowski E, Zimmer L, Gesierich A, Zierold S, French LE, Eigentler T, Amaral T, Heinzerling L (2024)
Publication Type: Journal article
Publication year: 2024
Journal
Book Volume: 203
Article Number: 114028
DOI: 10.1016/j.ejca.2024.114028
Abstract
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.
Authors with CRIS profile
Involved external institutions
Charité - Universitätsmedizin Berlin
Germany (DE)
Klinikum der Universität München
Germany (DE)
Universitätsklinikum Würzburg
Germany (DE)
Universitätsklinikum Carl Gustav Carus Dresden
Germany (DE)
Eberhard Karls Universität Tübingen
Germany (DE)
Johannes Wesling Klinikum Minden
Germany (DE)
Klinikum Ludwigshafen
Germany (DE)
Klinikum Dortmund
Germany (DE)
Universitätsklinikum Essen
Germany (DE)
Universitätsmedizin Rostock
Germany (DE)
Germany (DE)
Klinikum der Universität München
Germany (DE)
Universitätsklinikum Würzburg
Germany (DE)
Universitätsklinikum Carl Gustav Carus Dresden
Germany (DE)
Eberhard Karls Universität Tübingen
Germany (DE)
Johannes Wesling Klinikum Minden
Germany (DE)
Klinikum Ludwigshafen
Germany (DE)
Klinikum Dortmund
Germany (DE)
Universitätsklinikum Essen
Germany (DE)
Universitätsmedizin Rostock
Germany (DE)
How to cite
APA:
Ruf, T., Kramer, R., Forschner, A., Leiter, U., Meier, F., Reinhardt, L.,... Heinzerling, L. (2024). Second-line therapies for steroid-refractory immune-related adverse events in patients treated with immune checkpoint inhibitors. European Journal of Cancer, 203. https://doi.org/10.1016/j.ejca.2024.114028
MLA:
Ruf, Theresa, et al. "Second-line therapies for steroid-refractory immune-related adverse events in patients treated with immune checkpoint inhibitors." European Journal of Cancer 203 (2024).
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