TY - JOUR
T1 - Lower risk of severe checkpoint inhibitor toxicity in more advanced disease
AU - Verheijden, Rik J.
AU - May, Anne M.
AU - Blank, Christian U.
AU - van der Veldt, Astrid A. M.
AU - Boers-Sonderen, Marye J.
AU - Aarts, Maureen J. B.
AU - van den Berkmortel, Franchette W. P. J.
AU - van den Eertwegh, Alfonsus J. M.
AU - de Groot, Jan Willem B.
AU - van der Hoeven, Jacobus J. M.
AU - Hospers, Geke A. P.
AU - Piersma, Djura
AU - van Rijn, Rozemarijn S.
AU - ten Tije, Albert J.
AU - Vreugdenhil, Gerard
AU - van Zeijl, Michiel C. T.
AU - Wouters, Michel W. J. M.
AU - Haanen, John B. A. G.
AU - Kapiteijn, Ellen
AU - Suijkerbuijk, Karijn P. M.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - checkpoint inhibition
KW - immune-related adverse event (irAE)
KW - anti-PD1
KW - melanoma
KW - DMTR
KW - IMMUNE CHECKPOINTS
KW - ADVERSE EVENTS
KW - CANCER
KW - MELANOMA
KW - IPILIMUMAB
KW - IMMUNOTHERAPY
KW - ASSOCIATION
KW - MONOTHERAPY
KW - NIVOLUMAB
KW - SURVIVAL
U2 - 10.1136/esmoopen-2020-000945
DO - 10.1136/esmoopen-2020-000945
M3 - Article
C2 - 33199288
VL - 5
JO - ESMO Open
JF - ESMO Open
SN - 2059-7029
IS - 6
M1 - 000945
ER -