TY - JOUR
T1 - Association of blood biomarkers and autoimmunity with immune related adverse events in patients with cancer treated with immune checkpoint inhibitors
AU - Michailidou, Despina
AU - Khaki, Ali Raza
AU - Morelli, Maria Pia
AU - Diamantopoulos, Leonidas
AU - Singh, Namrata
AU - Grivas, Petros
N1 - Funding Information:
DM is supported by Pfizer US Pharmaceuticals Group grant, award number 53857367 (funder body did not have any role in this study). ARK is supported by the National Cancer Institute under training grant, award #T32CA009515. REDCap at ITHS is supported by National Center for Advancing Translational Sciences of National Institutes of Health under Award Number UL1 TR002319. LD acknowledges support from Kure It Cancer Research. NS acknowledges support from Rheumatology Research Foundation and American Heart Association. PG acknowledges support from Seattle Translational Tumor Research Program at Fred Hutchinson Cancer Research Center.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Patients with cancer treated with immune checkpoint inhibitors (ICIs) develop immune related adverse events (irAEs), however biomarkers are lacking. We hypothesized that clinicopathologic and laboratory factors would be associated with irAE risk and overall survival (OS) in this population. In a retrospective study of patients treated with ICIs we collected clinicopathologic, laboratory, irAEs and outcomes data. The association between baseline blood biomarkers, clinicopathologic features and irAEs was assessed by logistic regression adjusting for age, sex, smoking, cancer type, performance status, concomitant other systemic therapy, history of autoimmune disease (AD), chronic infection and pre-existing systemic steroid use (regardless of dose). Optimal cutoff values of biomarkers were identified by recursive partitioning analysis. 470 patients were identified; 156 (33%) developed irAEs, which were associated with baseline absolute lymphocyte count > 2.6 k/ul (adjusted [a]OR: 4.30), absolute monocyte count > 0.29 k/ul (aOR: 2.34) and platelet count > 145 k/ul (aOR: 2.23), neutrophil to lymphocyte ratio (NLR) ≤ 5.3 (aOR: 2.07) and monocyte to lymphocyte ratio (MLR) ≤ 0.73 (aOR: 2.96), as well as platelet to lymphocyte ratio ≤ 534 (aOR: 5.05). Patients with pre-existing AD (aOR: 2.57), family history of AD (aOR: 5.98), and ICI combination (aOR: 2.00) had higher odds of irAEs. Baseline NLR ≤ 5.3 (aHR: 0.68), MLR ≤ 0.73 (aHR: 0.43), PLT > 145 (aHR: 0.48) and PLR ≤ 534 (aHR: 0.48) were associated with longer OS. irAEs were associated with autoimmune history, ICI combination and baseline laboratory measurements. Lower NLR, MLR and PLR may have favorable prognostic value. Our hypothesis-generating findings require validation in larger prospective studies.
AB - Patients with cancer treated with immune checkpoint inhibitors (ICIs) develop immune related adverse events (irAEs), however biomarkers are lacking. We hypothesized that clinicopathologic and laboratory factors would be associated with irAE risk and overall survival (OS) in this population. In a retrospective study of patients treated with ICIs we collected clinicopathologic, laboratory, irAEs and outcomes data. The association between baseline blood biomarkers, clinicopathologic features and irAEs was assessed by logistic regression adjusting for age, sex, smoking, cancer type, performance status, concomitant other systemic therapy, history of autoimmune disease (AD), chronic infection and pre-existing systemic steroid use (regardless of dose). Optimal cutoff values of biomarkers were identified by recursive partitioning analysis. 470 patients were identified; 156 (33%) developed irAEs, which were associated with baseline absolute lymphocyte count > 2.6 k/ul (adjusted [a]OR: 4.30), absolute monocyte count > 0.29 k/ul (aOR: 2.34) and platelet count > 145 k/ul (aOR: 2.23), neutrophil to lymphocyte ratio (NLR) ≤ 5.3 (aOR: 2.07) and monocyte to lymphocyte ratio (MLR) ≤ 0.73 (aOR: 2.96), as well as platelet to lymphocyte ratio ≤ 534 (aOR: 5.05). Patients with pre-existing AD (aOR: 2.57), family history of AD (aOR: 5.98), and ICI combination (aOR: 2.00) had higher odds of irAEs. Baseline NLR ≤ 5.3 (aHR: 0.68), MLR ≤ 0.73 (aHR: 0.43), PLT > 145 (aHR: 0.48) and PLR ≤ 534 (aHR: 0.48) were associated with longer OS. irAEs were associated with autoimmune history, ICI combination and baseline laboratory measurements. Lower NLR, MLR and PLR may have favorable prognostic value. Our hypothesis-generating findings require validation in larger prospective studies.
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U2 - 10.1038/s41598-021-88307-3
DO - 10.1038/s41598-021-88307-3
M3 - Article
C2 - 33907229
AN - SCOPUS:85105083736
SN - 2045-2322
VL - 11
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 9029
ER -