Lower risk of severe checkpoint inhibitor toxicity in more advanced disease.

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.

• Authors: 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
• Journal: ESMO open (ESMO Open) Vol. 5 Issue 6 Pg. e000945 (11 2020) ISSN: 2059-7029 [Electronic] England
• PMID: 33199288 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.

Chemical References

• Antineoplastic Agents, Immunological
• Programmed Cell Death 1 Receptor

Topics

• Antineoplastic Agents, Immunological (therapeutic use)
• Female
• Humans
• Melanoma (drug therapy, epidemiology)
• Programmed Cell Death 1 Receptor
• Prospective Studies
• Retrospective Studies