Therapeutic and prognostic implications of immune-related adverse events in advanced non-small-cell lung cancer

• Verfasst von: Daniello, Lea [VerfasserIn]
• Verfasst von: Elshiaty, Mariam [VerfasserIn]
• Verfasst von: Bozorgmehr, Farastuk [VerfasserIn]
• Verfasst von: Kuon, Jonas [VerfasserIn]
• Verfasst von: Kazdal, Daniel [VerfasserIn]
• Verfasst von: Schindler, Hannah [VerfasserIn]
• Verfasst von: Shah, Rajiv [VerfasserIn]
• Verfasst von: Volckmar, Anna-Lena [VerfasserIn]
• Verfasst von: Lusky, Fabienne [VerfasserIn]
• Verfasst von: Diekmann, Leonore [VerfasserIn]
• Verfasst von: Liersch, Stephan [VerfasserIn]
• Verfasst von: Faehling, Martin [VerfasserIn]
• Verfasst von: Muley, Thomas [VerfasserIn]
• Verfasst von: Kriegsmann, Mark [VerfasserIn]
• Verfasst von: Gente, Karolina [VerfasserIn]
• Verfasst von: Stenzinger, Albrecht [VerfasserIn]
• Verfasst von: Thomas, Michael [VerfasserIn]
• Verfasst von: Christopoulos, Petros [VerfasserIn]
• Titel: Therapeutic and prognostic implications of immune-related adverse events in advanced non-small-cell lung cancer
• Verf.angabe: Lea Daniello, Mariam Elshiaty, Farastuk Bozorgmehr, Jonas Kuon, Daniel Kazdal, Hannah Schindler, Rajiv Shah, Anna-Lena Volckmar, Fabienne Lusky, Leonore Diekmann, Stephan Liersch, Martin Faehling, Thomas Muley, Mark Kriegsmann, Karolina Benesova, Albrecht Stenzinger, Michael Thomas and Petros Christopoulos
• E-Jahr: 2021
• Jahr: 29 June 2021
• Umfang: 14 S.
• Fussnoten: Gesehen am 05.08.2021
• Titel Quelle: Enthalten in: Frontiers in oncology
• Ort Quelle: Lausanne : Frontiers Media, 2011
• Jahr Quelle: 2021
• Band/Heft Quelle: 11(2021) vom: 29. Juni, Artikel-ID 703893, Seite 1-14
• ISSN Quelle: 2234-943X
• DOI: doi:10.3389/fonc.2021.703893
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: immune-checkpoint inhibitors
• Sach-SW: Immune-related adverse events
• Sach-SW: Immunotherapy
• Sach-SW: Lethality
• Sach-SW: prognosis
• Sach-SW: treatment interruption
• K10plus-PPN: 1765670160
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

Introduction: PD-(L)1 inhibitors have improved prognosis of non-small-cell lung cancer (NSCLC), but can also cause immune-related adverse events (irAE) that complicate management. Methods: We analyzed NSCLC patients receiving PD-(L)1 inhibitors from 2012-2020 in a German academic center. Results: IrAE showed comparable frequencies in stage IV (198/894 or 22%) vs. III (14/45 or 31%, p=0.15), after anti-PD-(L)1 monotherapy vs. chemoimmunotherapy (139/483 vs. 58/213, p=0.75), and across treatment lines. In stage IV, irAE occurred after 3.1 months in median, affected multiple organs (median 2) in 27/894 patients, and were associated with PD-L1 positivity (25% vs. 14%, p=0.003), lower neutrophil-to-lymphocyte ratios (29% vs. 17%, p3 months), and average cumulative prednisone doses >700 mg for all organs, except for skin. Patients developing irAE had longer progression-free (PFS) and overall survival (OS) in multivariable 12/14-week landmark analyses including ECOG status, treatment line, treatment type, PD-L1 TPS, and NLR (median PFS 17 vs. 10 months, HR=0.68, p=0.009; median OS 37 vs. 15 months, HR=0.40, p<0.001), regardless of grade. OS was longest with skin (95% at 2 years) and shortest with pneumonitis, hepatitis, neurologic and cardiologic irAE (38%, 37%, 28%, and 0% at 2 years, p<0.001). Conclusions: Approximately one-fourth of immunotherapy-treated NSCLC patients develop irAE, most of which necessitate treatment suspension and steroids. Despite occurring more frequently with PD-L1 positive tumors, lower NLR, and better ECOG PS, irAE are independently associated with longer survival, especially when affecting the skin. Lethality is below 1%.