Lower risk of severe checkpoint inhibitor toxicity in more advanced disease

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

doi:10.1136/esmoopen-2020-000945

Lower risk of severe checkpoint inhibitor toxicity in more advanced disease

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Article number	000945
Number of pages	6
Journal	ESMO Open
Volume	5
Issue number	6
DOIs	https://doi.org/10.1136/esmoopen-2020-000945
Publication status	Published - 2020

Keywords

checkpoint inhibition
immune-related adverse event (irAE)
anti-PD1
melanoma
DMTR
IMMUNE CHECKPOINTS
ADVERSE EVENTS
CANCER
MELANOMA
IPILIMUMAB
IMMUNOTHERAPY
ASSOCIATION
MONOTHERAPY
NIVOLUMAB
SURVIVAL

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Verheijden, R. J., May, A. M., Blank, C. U., van der Veldt, A. A. M., Boers-Sonderen, M. J., Aarts, M. J. B., van den Berkmortel, F. W. P. J., van den Eertwegh, A. J. M., de Groot, J. W. B., van der Hoeven, J. J. M., Hospers, G. A. P., Piersma, D., van Rijn, R. S., ten Tije, A. J., Vreugdenhil, G., van Zeijl, M. C. T., Wouters, M. W. J. M., Haanen, J. B. A. G., Kapiteijn, E., & Suijkerbuijk, K. P. M. (2020). Lower risk of severe checkpoint inhibitor toxicity in more advanced disease. ESMO Open, 5(6), Article 000945. https://doi.org/10.1136/esmoopen-2020-000945

@article{a0ad83014876498c8ec757dce75b7925,

title = "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.",

keywords = "checkpoint inhibition, immune-related adverse event (irAE), anti-PD1, melanoma, DMTR, IMMUNE CHECKPOINTS, ADVERSE EVENTS, CANCER, MELANOMA, IPILIMUMAB, IMMUNOTHERAPY, ASSOCIATION, MONOTHERAPY, NIVOLUMAB, SURVIVAL",

author = "Verheijden, {Rik J.} and May, {Anne M.} and Blank, {Christian U.} and {van der Veldt}, {Astrid A. M.} and Boers-Sonderen, {Marye J.} and Aarts, {Maureen J. B.} and {van den Berkmortel}, {Franchette W. P. J.} and {van den Eertwegh}, {Alfonsus J. M.} and {de Groot}, {Jan Willem B.} and {van der Hoeven}, {Jacobus J. M.} and Hospers, {Geke A. P.} and Djura Piersma and {van Rijn}, {Rozemarijn S.} and {ten Tije}, {Albert J.} and Gerard Vreugdenhil and {van Zeijl}, {Michiel C. T.} and Wouters, {Michel W. J. M.} and Haanen, {John B. A. G.} and Ellen Kapiteijn and Suijkerbuijk, {Karijn P. M.}",

note = "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: {\textcopyright} ",

year = "2020",

doi = "10.1136/esmoopen-2020-000945",

language = "English",

volume = "5",

journal = "ESMO Open",

issn = "2059-7029",

publisher = "BMJ Publishing Group",

number = "6",

}

Verheijden, RJ, May, AM, Blank, CU, van der Veldt, AAM, Boers-Sonderen, MJ, Aarts, MJB, van den Berkmortel, FWPJ, van den Eertwegh, AJM, de Groot, JWB, van der Hoeven, JJM, Hospers, GAP, Piersma, D, van Rijn, RS, ten Tije, AJ, Vreugdenhil, G, van Zeijl, MCT, Wouters, MWJM, Haanen, JBAG, Kapiteijn, E & Suijkerbuijk, KPM 2020, 'Lower risk of severe checkpoint inhibitor toxicity in more advanced disease', ESMO Open, vol. 5, no. 6, 000945. https://doi.org/10.1136/esmoopen-2020-000945

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 -