Delayed immune-related adverse events with anti-PD-1-based immunotherapy in melanoma

Abstract

Background: Immune-related adverse events (irAEs) typically occur within 4 months of starting anti-programmed cell death protein 1 (PD-1)-based therapy [anti-PD-1 ± anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4)], but delayed irAEs (onset > 12 months after commencement) can also occur. This study describes the incidence, nature and management of delayed irAEs in patients receiving anti-PD-1-based immunotherapy. Patients and methods: Patients with delayed irAEs from 20 centres were studied. The incidence of delayed irAEs was estimated as a proportion of melanoma patients treated with anti-PD-1-based therapy and surviving > 1 year. Onset, clinical features, management and outcomes of irAEs were examined. Results: One hundred and eighteen patients developed a total of 140 delayed irAEs (20 after initial combination with anti-CTLA4), with an estimated incidence of 5.3% (95% confidence interval 4.0-6.9, 53/999 patients at sites with available data). The median onset of delayed irAE was 16 months (range 12-53 months). Eighty-seven patients (74%) were on anti-PD-1 at irAE onset, 15 patients (12%) were < 3 months from the last dose and 16 patients (14%) were > 3 months from the last dose of anti-PD-1. The most common delayed irAEs were colitis, rash and pneumonitis; 55 of all irAEs (39%) were ≥ grade 3. Steroids were required in 80 patients (68%), as well as an additional immunosuppressive agent in 27 patients (23%). There were two irAE-related deaths: encephalitis with onset during anti-PD-1 and a multiple-organ irAE with onset 11 months after ceasing anti-PD-1. Early irAEs ( < 12 months) had also occurred in 69 patients (58%), affecting a different organ from the delayed irAE in 59 patients (86%). Conclusions: Delayed irAEs occur in a small but relevant subset of patients. Delayed irAEs are often different from previous irAEs, may be high grade and can lead to death. They mostly occur in patients still receiving anti-PD-1. The risk of delayed irAE should be considered when deciding the duration of treatment in responding patients. However, patients who stop treatment may also rarely develop delayed irAE.

RAS ID

38854

Document Type

Journal Article

Date of Publication

2021

Volume

32

Issue

7

Funding Information

National Health and Medical Research Council / University of Sydney Medical Foundation / Melanoma Institute Australia / Cancer Institute NSW Fellowship

PubMed ID

33798657

School

School of Medical and Health Sciences

Copyright

free_to_read

Publisher

Elsevier

Comments

Owen, C. N., Bai, X., Quah, T., Lo, S. N., Allayous, C., Callaghan, S., ... Menzies, A. M. (2021). Delayed immune-related adverse events with anti-PD-1-based immunotherapy in melanoma. Annals of Oncology, 32(7), 917-925. https://doi.org/10.1016/j.annonc.2021.03.204

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Link to publisher version (DOI)

10.1016/j.annonc.2021.03.204