Adverse Events in Anti-PD-1-Treated Adjuvant and First-Line Advanced Melanoma Patients

Daan Jan Willem Rauwerdink, Olivier van Not, Melissa de Meza, Remco van Doorn, Jos van der Hage, A J M van den Eertwegh, John B Haanen, Maureen J B Aarts, Franchette W P J van den Berkmortel, Christiaan U Blank, Marye J Boers-Sonderen, Jan Willem B de Groot, Geke A P Hospers, Djura Piersma, Rozemarijn S van Rijn, A M Stevense-den Boer, Astrid A M van der Veldt, Gerard Vreugdenhil, Michel W J M Wouters, Karijn P M SuijkerbuijkEllen Kapiteijn*

*Corresponding author for this work

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Abstract

Introduction: The difference in incidence and severity of anti-PD-1 therapy-related adverse events (irAEs) between adjuvant and advanced treated melanoma patients remains unclear, as no head-to-head studies have compared these groups. Methods: This multi-center cohort study analyzed melanoma patients treated with anti-PD-1 in adjuvant or advanced settings between 2015 and 2021. Comorbidities and ECOG performance status were assessed before treatment, and grade III-IV irAEs were monitored during treatment. Univariate and multivariate regression analyses were conducted to identify factors associated with irAE development. Results: A total of 1465 advanced melanoma patients and 908 resected melanoma patients received anti-PD-1 therapy. Adjuvant-treated patients were younger, with a median age of 63 years compared to 69 years in the advanced group ( p < 0.01), and had a better ECOG performance status ( p < 0.01). Comorbidities were seen more frequently in advanced melanoma patients than in those receiving adjuvant treatment, 76% versus 68% ( p < 0.01). Grade III-IV irAEs occurred in 214 (15%) advanced treated patients and in 119 (13%) adjuvant-treated patients. Multivariate analysis showed an increased risk of severe irAE development with the presence of any comorbidity (adjusted OR 1.22, 95% CI 1.02-1.44) and ECOG status greater than 1 (adjusted OR 2.00, 95% CI 1.20-3.32). Adjuvant therapy was not associated with an increased risk of irAE development compared to advanced treatment (adjusted OR 0.95, 95% CI 0.74-1.21) after correcting for comorbidities and ECOG performance score. Anti-PD-1 therapy was halted due to toxicity (any grade irAE) more often in the adjuvant setting than in the advanced setting, 20% versus 15% ( p < 0.01). Conclusions: Higher ECOG performance status and presence of any comorbidity were independently associated with an increased risk of Grade III-IV irAE in adjuvant and advanced treated melanoma patients. Patients treated in the adjuvant setting did not have an increased risk of developing severe irAEs compared to advanced melanoma patients. These findings are of clinical significance in consulting patients for adjuvant anti-PD-1 treatment.

Original languageEnglish
Article number2656
Number of pages13
JournalCancers
Volume16
Issue number15
DOIs
Publication statusPublished - 26 Jul 2024

Keywords

  • immune checkpoint inhibitors
  • melanoma
  • side-effects

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