Late-onset and long-lasting immune-related adverse events from immune checkpoint-inhibitors: An overlooked aspect in immunotherapy.

Details

Serval ID
serval:BIB_4791AD7F437D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Late-onset and long-lasting immune-related adverse events from immune checkpoint-inhibitors: An overlooked aspect in immunotherapy.
Journal
European journal of cancer
Author(s)
Ghisoni E., Wicky A., Bouchaab H., Imbimbo M., Delyon J., Gautron Moura B., Gérard C.L., Latifyan S., Özdemir B.C., Caikovski M., Pradervand S., Tavazzi E., Gatta R., Marandino L., Valabrega G., Aglietta M., Obeid M., Homicsko K., Mederos Alfonso N.N., Zimmermann S., Coukos G., Peters S., Cuendet M.A., Di Maio M., Michielin O.
ISSN
1879-0852 (Electronic)
ISSN-L
0959-8049
Publication state
Published
Issued date
05/2021
Peer-reviewed
Oui
Volume
149
Pages
153-164
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy but frequently cause immune-related adverse events (irAEs). Description of late-onset and duration of irAEs in the literature is often incomplete.
To investigate reporting and incidence of late-onset and long-lasting irAEs, we reviewed all registration trials leading to ICI's approval by the US FDA and/or EMA up to December 2019. We analysed real-world data from all lung cancer (LC) and melanoma (Mel) patients treated with approved ICIs at the University Hospital of Lausanne (CHUV) from 2011 to 2019. To account for the immortal time bias, we used a time-dependent analysis to assess the potential association between irAEs and overall survival (OS).
Duration of irAEs and proportion of patients with ongoing toxicities at data cut-off were not specified in 56/62 (90%) publications of ICIs registration trials. In our real-world analysis, including 437 patients (217 LC, 220 Mel), 229 (52.4%) experienced at least one grade ≥2 toxicity, for a total of 318 reported irAEs, of which 112 (35.2%) were long-lasting (≥6 months) and about 40% were ongoing at a median follow-up of 369 days [194-695] or patient death. The cumulative probability of irAE onset from treatment initiation was 42.8%, 51.0% and 57.3% at 6, 12 and 24 months, respectively. The rate of ongoing toxicity from the time of first toxicity onset was 42.8%, 38.4% and 35.7% at 6, 12 and 24 months. Time-dependent analysis showed no significant association between the incidence of irAEs and OS in both cohorts (log Rank p = 0.67 and 0.19 for LC and Mel, respectively).
Late-onset and long-lasting irAEs are underreported but common events during ICIs therapy. Time-dependent survival analysis is advocated to assess their impact on OS. Real-world evidence is warranted to fully capture and characterise late-onset and long-lasting irAEs in order to implement appropriate strategies for patient surveillance and follow-up.
Keywords
Immortal time bias, Immune-checkpoint inhibitors, Immune-related adverse events, Late-onset toxicities, Long-lasting toxicities
Pubmed
Web of science
Open Access
Yes
Create date
25/05/2021 10:57
Last modification date
05/06/2021 6:33
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