Lower risk of severe checkpoint inhibitor toxicity in more advanced disease

Rik J Verheijden, Anne M May, Christian U Blank, Astrid A M van der Veldt, Marye J Boers-Sonderen, Maureen J B Aarts, Franchette W P J van den Berkmortel, Alfonsus J M van den Eertwegh, Jan Willem B de Groot, Jacobus J M van der Hoeven, Geke A P Hospers, Djura Piersma, Rozemarijn S van Rijn, Albert J Ten Tije, Gerard Vreugdenhil, Michiel C T van Zeijl, Michel W J M Wouters, John B A G Haanen, Ellen Kapiteijn, Karijn P M Suijkerbuijk

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Abstract

BACKGROUND: Immune checkpoint inhibitor (ICI) can cause severe and sometimes fatal immune-related adverse events (irAEs). Since these irAEs mimick immunological disease, a female predominance has been speculated on. Nevertheless, no demographic or tumour-related factors associated with an increased risk of irAEs have been identified until now.

METHODS: Risk ratios of severe (grade ≥3) irAEs for age, sex, WHO performance status, number of comorbidities, stage of disease, number of metastases and serum lactate dehydrogenases (LDH) were estimated using data from anti-PD1-treated patients with advanced melanoma in the prospective nationwide Dutch Melanoma Treatment Registry.

RESULTS: 111 (11%) out of 819 anti-programmed cell death 1 treated patients experienced severe irAEs. Patients with non-lung visceral metastases (stage IV M1c or higher) less often experienced severe irAEs (11%) compared with patients with only lung and/or lymph node/soft tissue involvement (stage IV M1b or lower; 19%; adjusted risk ratio (RRadj) 0.63; 95% CI 0.41 to 0.94). Patients with LDH of more than two times upper limit of normal had a non-significantly lower risk of developing severe irAEs than those with normal LDH (RRadj 0.65; 95% CI 0.20 to 2.13). None of the other variables were associated with severe irAEs.

CONCLUSION: In patients with melanoma, more advanced disease is associated with a lower rate of severe irAEs. No association with sex was found.

Original languageEnglish
Article number000945
Pages (from-to)e000945
JournalESMO open
Volume5
Issue number6
DOIs
Publication statusPublished - Nov 2020

Keywords

  • anti-PD1
  • checkpoint inhibition
  • DMTR
  • immune-related adverse event (irAE)
  • melanoma

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