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.
N1 - Funding Information:
Funding The Netherlands Organisation for Health Research and Development funded the start-up of the Dutch Melanoma Treatment Registry (DMTR). Grant number: 836 002 002. This grant was awarded under the effectiveness research for high-cost medicine programme. From its foundation, the DMTR has been sponsored by BMS, Novartis, Roche Nederland BV, MSD and Pierre Fabre via the Dutch Institute for Clinical Auditing (DICA).
Funding Information:
The Netherlands Organisation for Health Research and Development funded the start-up of the Dutch Melanoma Treatment Registry (DMTR). Grant number: 836 002 002. This grant was awarded under the effectiveness research for high-cost medicine programme. From its foundation, the DMTR has been sponsored by BMS, Novartis, Roche Nederland BV, MSD and Pierre Fabre via the Dutch Institute for Clinical Auditing (DICA).
Funding Information:
Competing interests CUB reports receiving commercial research grants from
Publisher Copyright:
©
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
SN - 2059-7029
VL - 5
JO - ESMO Open
JF - ESMO Open
IS - 6
M1 - 000945
ER -