ESMO Open (Dec 2020)

Lower risk of severe checkpoint inhibitor toxicity in more advanced disease

  • Anne M May,
  • Michel W J M Wouters,
  • Ellen Kapiteijn,
  • John B A G Haanen,
  • Christian U Blank,
  • Maureen J B Aarts,
  • Rik J Verheijden,
  • Astrid A M van der Veldt,
  • Marye J Boers-Sonderen,
  • 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,
  • Karijn P M Suijkerbuijk

DOI
https://doi.org/10.1136/esmoopen-2020-000945
Journal volume & issue
Vol. 5, no. 6

Abstract

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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.