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Multicenter Study
. 2021 May 1;7(5):744-748.
doi: 10.1001/jamaoncol.2021.0051.

Chronic Immune-Related Adverse Events Following Adjuvant Anti-PD-1 Therapy for High-risk Resected Melanoma

J Randall Patrinely Jr  1 , Rebecca Johnson  2   3 , Aleigha R Lawless  4 , Prachi Bhave  2   5 , Amelia Sawyers  6 , Maya Dimitrova  7 , Hui Ling Yeoh  8 , Marisa Palmeri  9 , Fei Ye  10 , Run Fan  10 , Elizabeth J Davis  11 , Suthee Rapisuwon  12 , Georgina V Long  2   3 , Andrew Haydon  8 , Iman Osman  7 , Janice M Mehnert  7   9 , Matteo S Carlino  5 , Ryan J Sullivan  4 , Alexander M Menzies  2   3 , Douglas B Johnson  11
Affiliations
Multicenter Study

Chronic Immune-Related Adverse Events Following Adjuvant Anti-PD-1 Therapy for High-risk Resected Melanoma

J Randall Patrinely Jr et al. JAMA Oncol. .

Erratum in

  • Error in Funding/Support.
    [No authors listed] [No authors listed] JAMA Oncol. 2021 May 1;7(5):785. doi: 10.1001/jamaoncol.2021.1616. JAMA Oncol. 2021. PMID: 34014308 Free PMC article. No abstract available.

Abstract

Importance: Agents targeting programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) improve long-term survival across many advanced cancers and are now used as adjuvant therapy for resected stage III and IV melanomas. The incidence and spectrum of chronic immune-related adverse events (irAEs) have not been well defined.

Objective: To determine the incidence, time course, spectrum, and associations of chronic irAEs arising from adjuvant anti-PD-1 therapy.

Design, setting, and participants: This retrospective multicenter cohort study was conducted between 2015 and 2020 across 8 academic medical centers in the United States and Australia. Patients with stage III to IV melanomas treated with anti-PD-1 in the adjuvant setting were included.

Main outcomes and measures: Incidence, types, and time course of chronic irAEs (defined as irAEs persisting at least 12 weeks after therapy cessation).

Results: Among 387 patients, the median (range) age was 63 (17-88) years, and 235 (60.7%) were male. Of these patients, 267 (69.0%) had any acute irAE, defined as those arising during treatment with anti-PD-1, including 52 (19.5%) with grades 3 through 5 events; 1 patient each had fatal myocarditis and neurotoxicity. Chronic irAEs, defined as those that persisted beyond 12 weeks of anti-PD-1 discontinuation, developed in 167 (43.2%) patients, of which most (n = 161; 96.4%) were mild (grade 1 or 2) and most persisted until last available follow-up (n = 143; 85.6%). Endocrinopathies (73 of 88; 83.0%), arthritis (22 of 45; 48.9%), xerostomia (9 of 17; 52.9%), neurotoxicities (11 of 15; 73.3%), and ocular events (5 of 8; 62.5%) were particularly likely to become chronic. In contrast, irAEs affecting visceral organs (liver, colon, lungs, kidneys) had much lower rates of becoming chronic irAEs; for example, colitis became chronic in 6 of 44 (13.6%) cases, of which 4 of 6 (66.7%) resolved with prolonged follow-up. Age, gender, time of onset, and need for steroids were not associated with the likelihood of chronicity of irAEs.

Conclusion and relevance: In this multicenter cohort study, chronic irAEs associated with anti-PD-1 therapy appear to be more common than previously recognized and frequently persisted even with prolonged follow-up, although most were low grade. The risks of chronic irAEs should be integrated into treatment decision-making.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Johnson serves on advisory boards for Array Biopharma, Bristol Myers Squibb, Iovance, Janssen, Merck, OncoSec, and Novartis, and receives research funding from Bristol Myers Squibb and Incyte. Dr Haydon serves on advisory boards for Novartis, Bristol Myers Squibb, MSD, and Pierre Fabre. Dr Carlino has served on advisory boards for Bristol Myers Squibb, MSD, Amgen, Novartis, Pierre Fabre, Roche, Sanofi, Merck, Ideaya Biosciences, Regeneron, Nektar, Eisai, and QBiotics, and receives honoraria from Bristol Myers Squibb, MSD, and Novartis. Dr Sullivan serves on advisory boards for Asana BioSciences, Bristol Myers Squibb, Novartis, Pfizer, Iovance, Eisai, and Merck, and has received research funding from Amgen and Merck. Dr Bhave has received travel support from MSD. Dr Menzies has served on advisory boards for Bristol Myers Squibb, MSD, Novartis, Roche, Pierre Fabre, and QBiotics. Ms Johnson has received honoraria from MSD. Dr Davis receives research funding from BMS, Karyopharm, Five Prime Therapeutics, Genentech, Actuate, Incyte, and Top Alliance Biosciences. Dr Long is a consultant advisor for Array BioPharma, Aduro, Amgen, Boehringer Ingelheim International, Bristol Myers Squibb, Highlight Therapeutics, MassArray, Merck, MSD, Novartis, OncoSec Medical, Pierre Fabre, Regeneron Pharmaceuticals, Roche, QBiotics, SkylineDx, and Sandoz. Dr Mehnert receives personal fees from Regeneron and Bristol Myers Squibb, as well as grants from Incyte and Merck. Dr Rapisuwon receives grants from Bristol Myers Squibb. No other disclosures were reported.

Figures

Figure.
Figure.. Kaplan-Meier Estimates of Overall Survival (OS) and Relapse-Free Survival (RFS)
irAEs indicates immune-related adverse events.
See this image and copyright information in PMC

Comment in

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