Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Oct 1;34(5):439-449.
doi: 10.1097/CMR.0000000000000985. Epub 2024 Jul 1.

Exploring the clinical significance of specific immune-related adverse events in melanoma patients undergoing immune checkpoint inhibitor therapy

Nethanel Asher  1 , Neta Bar-Hai  2 , Guy Ben-Betzalel  2 , Ronen Stoff  2 , Shirly Grynberg  2 , Jacob Schachter  2   3 , Ronnie Frommer-Shapira  2
Affiliations

Exploring the clinical significance of specific immune-related adverse events in melanoma patients undergoing immune checkpoint inhibitor therapy

Nethanel Asher et al. Melanoma Res. .

Abstract

Several studies have demonstrated that patients who experience immune-related adverse events (irAE) as a result of immunotherapy treatment, exhibit significantly improved outcomes compared to patients without toxicity. Data regarding the impact of specific irAE is, however, currently lacking. This is a real-world single-site cohort of 415 advanced melanoma patients who were treated with immunotherapy as first-line between 2014 and 2020, with a median follow-up of 24.5 months. The most frequent irAEs were cutaneous (classified as non-vitiligo, n = 110, 26.5% and vitiligo, n = 48, 11.6%), rheumatologic ( n = 68, 16.4%), gastrointestinal ( n = 66, 15.9%), endocrine ( n = 61, 14.7%), and hepatitis ( n = 50, 12%). Specific irAE that were significantly associated with survival benefit were rheumatologic (hazard ratio 0.34 for PFS, P < 0.001; hazard ratio 0.38 for OS, P < 0.001), non-vitiligo cutaneous (hazard ratio 0.58 for PFS, P < 0.001; hazard ratio 0.54 for OS, P = 0.001), vitiligo (hazard ratio 0.30 for PFS, P < 0.001; hazard ratio 0.29 for OS, P < 0.001), and endocrine (hazard ratio 0.6 for PFS, P = 0.01; hazard ratio 0.52 for OS, P < 0.001). Other types of irAEs, such as colitis, hepatitis and others - do not present this correlation. The occurrence of these specific irAEs may reflect a hyperactivated immune response and thus can serve as meaningful clinical biomarkers.

PubMed Disclaimer

References

    1. Hodi FS, Chiarion -Sileni V, Lewis KD, Grob J, Rutkowski P, Lao CD, et al. Long-term survival in advanced melanoma for patients treated with nivolumab plus ipilimumab in CheckMate 067. J Clin Oncol 2022; 40 (16_suppl):9522–9522.
    1. Robert C, Carlino MS, McNeil C, Ribas A, Grob J-J, Schachter J, et al. Seven-year follow-up of the phase III KEYNOTE-006 study: pembrolizumab versus ipilimumab in advanced melanoma. J Clin Oncol 2023; 41:3998–4003.
    1. Tawbi HA, Schadendorf D, Lipson EJ, Ascierto PA, Matamala L, Castillo Gutiérrez E, et al. Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma. N Engl J Med 2022; 386:24–34.
    1. Nakamura Y. Biomarkers for immune checkpoint inhibitor-mediated tumor response and adverse events. Front Med 2019; 66:119–119.
    1. Taylor J, Gandhi A, Gray E, Zaenker P. Checkpoint inhibitor immune-related adverse events: a focused review on autoantibodies and B cells as biomarkers, advancements and future possibilities. Front Immunol 2023; 13:991433.

Substances