Lower risk of severe checkpoint inhibitor toxicity in more advanced disease

ESMO Open

article

Rik J. Verheijden¹  Anne M. May²  Christian U. Blank³  Astrid A.M. van der Veldt⁴  Marye J. Boers-Sonderen¹  Maureen J.B. Aarts¹  Franchette W.P.J. van den Berkmortel⁵  Alfonsus J.M. van den Eertwegh⁶  Jan Willem B. de Groot⁷  Jacobus J.M. van der Hoeven¹  Geke A.P. Hospers⁸  Djura Piersma⁹  Rozemarijn S. van Rijn^1,10  Albert J. ten Tije^1,11  Gerard Vreugdenhil^1,12  Michiel C.T. van Zeijl^1,13  Michel W.J.M. Wouters^1,14  John B.A.G. Haanen^1,16  Ellen Kapiteijn^1,13  Karijn P.M. Suijkerbuijk¹ 

[1] Department of Medical Oncology;University Medical Center Utrecht;Department of Medical Oncology and Division of Molecular Oncology & Immunology, The Netherlands Cancer Institute;Departments of Medical Oncology and Radiology & Nuclear Medicine;Department of Medical Oncology, Zuyderland Medical Centre Sittard-Geleen;Department of Medical Oncology, Cancer Center Amsterdam;Oncology Center Isala;Department of Medical Oncology, University Medical Centre Groningen;Department of Internal Medicine;Department of Internal Medicine, Medical Centre Leeuwarden;Department of Internal Medicine, Amphia Hospital;Department of Internal Medicine, Maxima Medical Centre;Department of Medical Oncology, Leiden University Medical Center;Scientific Bureau, Dutch Institute for Clinical Auditing;Department of Medical and Surgical Oncology, The Netherlands Cancer Institute;Department of Medical Oncology, The Netherlands Cancer Institute

关键词: checkpoint inhibition;    immune-related adverse event (irAE);    anti-PD1;    melanoma;    DMTR;   

DOI  :  10.1136/esmoopen-2020-000945

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

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.

【 授权许可】

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