Abstract 5044
Background
Cisplatin is a widely used chemotherapeutic agent for multiple indications. Unfortunately, in a substantial set of patients treated with cisplatin acute kidney injury (AKI) occurs. A recent case report suggested single nucleotide polymorphisms (SNPs) in the COMT gene might be associated with increased cisplatin-induced nephrotoxicity (de Jong et al., BJCP, 2017). Here, we assessed the association of 3 SNPs in this gene with cisplatin-induced nephrotoxicity in our patient population.
Methods
Whole blood samples and serum creatinine concentrations (Scr) of 556 patients who received cisplatin between 2005-2019 were available. The 1947 G>A (Val158Met, rs4680), c.615 + 310 C>T (rs4646316) and c.616 – 367 C>T (rs9332377) SNPs were associated with AKI (CTCAE v4.03) using Fisher’s exact test and difference in Scr up to 2 weeks prior to and up to 6 weeks after cisplatin treatment was described.
Results
Median Scr at baseline was 70 μmol/l (inter quartile range (IQR) 59-81). Up to six weeks after the start of cisplatin treatment the median increased to 81 μmol/l (IQR 69-96). The presence of a variant of c.615 + 310C>T was associated with an increased occurrence of AKI ≥ grade 3 toxicity in patients carrying a homozygous variant (Var) compared to wildtype (WT) patients. AKI grade ≥ 3 occurred in 4 out of 31 (13%) homozygous variant patients against 6 out of 317 (2%) patients carrying wildtype alleles (p = 0.005) after correction for age in a multivariable model. Dehydration occurred in 14 of the 16 patients with AKI grade 3 (3 of 4 WT, 6 of 6 HT and 5 of 6 Var) and likely is a confounding factor. The remaining SNPs were not significantly associated with AKI or difference in Scr.
Conclusions
This study showed that variation in COMT c.615 + 310 C>T (rs4646316) potentially affects the development of AKI grade ≥3, although these results appear to be confounded by dehydration. Therefore, the value of this finding for daily practice is currently unclear and needs to be explored in a prospective setting.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
R.H.J. Mathijssen.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3349 - Interplay between miR-17-5p and MALAT-1 Shapes The Cytokine Storm in Triple Negative Breast Cancer (TNBC) Tumor Microenvironment
Presenter: Raghda Soliman
Session: Poster Display session 3
Resources:
Abstract
4014 - Clinical verification on the relationship between lipid metabolism and the immune microenvironment of breast cancer
Presenter: Wataru Goto
Session: Poster Display session 3
Resources:
Abstract
4158 - The clinical and transcriptional signatures of human CD204 reveal an applicable marker for tumor associated macrophage in breast cancer
Presenter: Yunjie He
Session: Poster Display session 3
Resources:
Abstract
5392 - Activated effector T cells co-expressing multiple inhibitory receptors (IRs) are enriched in the tumor immune microenvironment in high grade serous ovarian cancer (HGSOC)
Presenter: Alice Bergamini
Session: Poster Display session 3
Resources:
Abstract
2617 - Oncolytic reovirus as a new anti-tumor strategy in castration resistant prostate cancer
Presenter: Yunlim Kim
Session: Poster Display session 3
Resources:
Abstract
2995 - Dysregulation of helper T lymphocytes in esophageal squamous cell carcinoma (ESCC) patients is highly associated with aberrant production of miR-21
Presenter: Ali Memarian
Session: Poster Display session 3
Resources:
Abstract
3597 - Myeloid derived suppressor cells but not regulatory T cells are associated with adaptive immunity and clinical outcomes in anal squamous cell carcinoma
Presenter: Christophe Borg
Session: Poster Display session 3
Resources:
Abstract
3430 - Evaluation of immune responses among responders (R) and non-responders (non-R) in a humanized mouse model with colorectal cancer (CRC) xenografts treated with combination immunotherapy
Presenter: Juan Marín Jiménez
Session: Poster Display session 3
Resources:
Abstract
1995 - ¬¬Advanced melanoma patients with high CD16+ macrophages have better response and survival to anti-PD-1 based immunotherapy
Presenter: Hansol Lee
Session: Poster Display session 3
Resources:
Abstract
3988 - Basal NK activity and early Treg function inhibition predicts Nivolumab responsiveness in metastatic renal cancer patients (REVOLUTION) trial.
Presenter: Sara Santagata
Session: Poster Display session 3
Resources:
Abstract