Serum immune modulators associated with immune-related toxicities and efficacy of atezolizumab in patients with non-small cell lung cancer.
Atezolizumab
B cell-activating factor (BAFF)
Immune-related adverse events (irAEs)
Inducible T cell co-stimulator (ICOS)
Non-small cell lung cancer
Serum immune modulators
Journal
Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060
Informations de publication
Date de publication:
Jul 2023
Jul 2023
Historique:
received:
22
04
2022
accepted:
06
07
2022
medline:
5
7
2023
pubmed:
15
7
2022
entrez:
14
7
2022
Statut:
ppublish
Résumé
Identifying patients at high risk of immune-related adverse events (irAEs) that impede the achievement of durable efficacy of programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) blockade therapy is important in improving their management. Identification of a novel predictive factor of therapeutic benefit is also important in improving patient selection for treatment with PD-1/PD-L1 inhibitors. Further determinants driving response and linking with irAEs are urgently required. To address these unmet needs in the field, we explored whether 27 soluble checkpoint proteins and immunomodulatory proteins in serum at the therapy baseline and after week 3 were associated with irAE onset and therapeutic efficacy using MILLIPLEX Human Immuno-Oncology Checkpoint Protein Panel assays in a prospective, multicenter cohort of 81 patients with non-small cell lung cancer (NSCLC) receiving atezolizumab monotherapy. By competing-risks regression analysis, we identified that high levels of B cell-activating factor (BAFF) at baseline were a significant and strong risk factor of irAEs (hazard ratio, 5.61; 95% confidence interval, 2.43-12.96; P < 0.0001). We also identified that increased inducible T cell co-stimulator (ICOS) during the first therapeutic cycle was an independent factor associated with prolonged progression-free survival and overall survival. These findings are in keeping with the reported mechanistic basis of these molecules and may provide potential guidance for clinical decision-making to improve patient care. Further validation studies are warranted. Trial registration UMIN000035616 (January 28, 2019).
Identifiants
pubmed: 35834011
doi: 10.1007/s00432-022-04193-w
pii: 10.1007/s00432-022-04193-w
doi:
Substances chimiques
atezolizumab
52CMI0WC3Y
Programmed Cell Death 1 Receptor
0
Immunologic Factors
0
B7-H1 Antigen
0
Types de publication
Multicenter Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2963-2974Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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