Lower risk of severe checkpoint inhibitor toxicity in more advanced disease. Issue 6 (16th November 2020)

• Record Type: Journal Article
• Authors: Verheijden, Rik J; May, Anne M; Blank, Christian U; van der Veldt, Astrid A M; Boers-Sonderen, Marye J; Aarts, Maureen J B; van den Berkmortel, Franchette W P J; van den Eertwegh, Alfonsus J M; de Groot, Jan Willem B; van der Hoeven, Jacobus J M; Hospers, Geke A P; Piersma, Djura; van Rijn, Rozemarijn S; ten Tije, Albert J; Vreugdenhil, Gerard; van Zeijl, Michiel C T; Wouters, Michel W J M; Haanen, John B A G; Kapiteijn, Ellen; Suijkerbuijk, Karijn P M
• Is Part Of: ESMO open. Volume 5:Issue 6(2020)
• Publication Date: 2020-11-16
• Subjects: checkpoint inhibition -- immune-related adverse event (irAE) -- anti-PD1 -- melanoma -- DMTR; Cancer -- Periodicals; 616.994005
• DOI: 10.1136/esmoopen-2020-000945
• Languages: English
• ISSNs: 2059-7029

Abstract

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.