Adjuvant immunotherapy in older patients with stage III and resected stage IV melanoma: Toxicity and recurrence-free survival outcomes from the Dutch melanoma treatment registry

A Özkan, E Kapiteijn, F van den Bos, M J B Aarts, F W P J van den Berkmortel, C U Blank, M Bloem, W A M Blokx, M J Boers-Sonderen, J J Bonenkamp, A J M van den Eertwegh, J W B de Groot, J B Haanen, C E Holtslag, G A P Hospers, D Piersma, R S van Rijn, A M Stevense-den Boer, K P M Suijkerbuijk, A A M van der VeldtG Vreugdenhil, M W J M Wouters, J E A Portielje, N A de Glas

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: Adjuvant anti-PD-1 therapy improves relapse free survival in stage III melanoma, but also leads to immune-related adverse events (irAEs). Older patients are of particular interest due to comorbidities and frailty, which may impact their ability to tolerate irAEs and benefit from anti-PD-1 therapy. This study aimed to explore associations between clinical parameters and the occurrence of grade ≥ 3 irAEs and recurrence-free survival (RFS) in older patients with radically resected stage III/IV cutaneous melanoma treated with adjuvant anti-PD-1 therapy.

METHODS: Patients aged ≥ 65 with resected stage III/IV cutaneous melanoma treated with adjuvant anti-PD-1 therapy between 2018 and 2022 were selected using real-world data from the nationwide Dutch Melanoma Treatment Registry (DMTR). A univariate and multivariable logistic regression was used to compare determinants of grade ≥ 3 irAEs, and univariate and multivariable Cox-proportional hazard models were fitted to identify factors influencing RFS.

RESULTS: The study included 885 patients, with 280 aged 75 and older. The incidence of grade ≥ 3 irAEs was 15.5 % in the 65-74 age group and 13.9 % in the ≥ 75 age group. No significant correlation was found between age and grade ≥ 3 irAEs. However, an increasing number of comorbidities was associated with a higher risk of grade ≥ 3 irAEs (multivariable analyses: OR 1.83, 95 % C.I. 0.99-3.40). The 1-year RFS rate of 80.0 % of this study was comparable to those reported in previous registration trials and real-world data. Having ≥ 3 comorbidities was significantly associated with a decrease in RFS (HR: 1.68, 95 % C.I. 1.15-2.44).

CONCLUSION: Older patients had similar benefit of adjuvant immunotherapy compared to older subgroups in previous trials. However, patients with multiple comorbidities were at increased risk of grade ≥ 3 irAEs and had a lower RFS. This should be considered when deciding upon adjuvant treatment.

Original languageEnglish
Article number115056
JournalEuropean Journal of Cancer
Volume212
Early online date30 Sept 2024
DOIs
Publication statusPublished - Nov 2024

Keywords

  • Immune checkpoint inhibitors
  • Immune-related adverse events
  • Melanoma
  • Oncology
  • Recurrence-free survival

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