Combined use of tyrosine kinase inhibitors with PD-(L)1 blockade increased the risk of thyroid dysfunction in PD-(L)1 blockade: a prospective study.

Humans Male Female Prospective Studies Middle Aged Protein Kinase Inhibitors / adverse effects Aged B7-H1 Antigen / antagonists & inhibitors Immune Checkpoint Inhibitors / adverse effects Thyroid Diseases / chemically induced Adult Incidence Neoplasms / drug therapy Aged, 80 and over Hypothyroidism / chemically induced Tyrosine Kinase Inhibitors

Hypothyroidism PD-1 PD-L1 TKI Thyroiditis irAE

Journal

Cancer immunology, immunotherapy : CII

ISSN: 1432-0851

Titre abrégé: Cancer Immunol Immunother

Pays: Germany

ID NLM: 8605732

Informations de publication

Date de publication:
04 Jun 2024

Historique:

received: 28 03 2024

accepted: 13 05 2024

medline: 4 6 2024

pubmed: 4 6 2024

entrez: 4 6 2024

Statut: epublish

Résumé

Anti-programmed cell death-1 (ligand-1) antibody [PD-(L)1-Ab] can cause destructive thyroiditis and/or hypothyroidism. In addition, tyrosine kinase inhibitors (TKIs) frequently induce hypothyroidism. The aim of this prospective study is to examine the incidence and clinical characteristics of thyroid dysfunction induced by combination therapy of a PD-(L)1-Ab and TKI [PD-(L)1-Ab/TKI]. A total of 757 patients treated with PD-(L)1-Ab or PD-(L)1-Ab/TKI were evaluated for anti-thyroid antibodies (ATAs) at baseline and for thyroid function for 48 weeks after treatment initiation and then observed until the last visit. The cumulative incidences of destructive thyroiditis [4/23 (17.4%) vs. 45/734 (6.1%) patients, p < 0.001], isolated hypothyroidism [10/23 (43.5%) vs. 29/734 (4.0%) patients, p < 0.001], and all thyroid dysfunction [14/23 (60.9%) vs. 74/734 (10.1%) patients, p < 0.001] were significantly higher in the PD-(L)1-Ab/TKI group than PD-(L)1-Ab group, respectively. All patients positive for ATAs at baseline developed thyroid dysfunction after PD-(L)1-Ab/TKI treatment, a significantly higher incidence than that in those negative for ATAs at baseline [4/4 (100%) vs. 10/19 (52.6%) patients, p = 0.026]. The addition of TKIs increased the risk of thyroid dysfunction induced by PD-(L)1-Ab, with the risk being higher in patients positive for baseline ATAs.

Sections du résumé

BACKGROUND BACKGROUND

METHODS METHODS

A total of 757 patients treated with PD-(L)1-Ab or PD-(L)1-Ab/TKI were evaluated for anti-thyroid antibodies (ATAs) at baseline and for thyroid function for 48 weeks after treatment initiation and then observed until the last visit.

RESULTS RESULTS

The cumulative incidences of destructive thyroiditis [4/23 (17.4%) vs. 45/734 (6.1%) patients, p < 0.001], isolated hypothyroidism [10/23 (43.5%) vs. 29/734 (4.0%) patients, p < 0.001], and all thyroid dysfunction [14/23 (60.9%) vs. 74/734 (10.1%) patients, p < 0.001] were significantly higher in the PD-(L)1-Ab/TKI group than PD-(L)1-Ab group, respectively. All patients positive for ATAs at baseline developed thyroid dysfunction after PD-(L)1-Ab/TKI treatment, a significantly higher incidence than that in those negative for ATAs at baseline [4/4 (100%) vs. 10/19 (52.6%) patients, p = 0.026].

CONCLUSIONS CONCLUSIONS

The addition of TKIs increased the risk of thyroid dysfunction induced by PD-(L)1-Ab, with the risk being higher in patients positive for baseline ATAs.

Identifiants

DOI: 10.1007/s00262-024-03733-2 PMID: 38833157

pubmed: 38833157

doi: 10.1007/s00262-024-03733-2

pii: 10.1007/s00262-024-03733-2

doi:

Substances chimiques

Protein Kinase Inhibitors 0

B7-H1 Antigen 0

Immune Checkpoint Inhibitors 0

CD274 protein, human 0

Tyrosine Kinase Inhibitors 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

146

Informations de copyright

Références

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