Background: Treatment with PD-1 inhibitors can be hampered by severe auto-immune-related toxicities. Our objective was to identify single-nucleotide polymorphisms (SNPs) in genes previously associated with auto-immunity, which are associated with toxicities in nivolumab-treated NSCLC patients. This was in order to identify patients prone to develop severe toxicities and to gain more insight into the underlying pathobiology.
Methods: We analysed 322 nivolumab-treated patients and assessed the association with toxicities for seven SNPs in four genes, which are considered contributors to PD-1-directed T-cell responses, i.e., PDCD1, PTPN11, ZAP70 and IFNG. Every SNP was tested for its association with toxicity endpoints. Significant associations were tested in a validation cohort.
Results: A multivariable analysis in the exploration cohort showed that homozygous variant patients for PDCD1 804C>T (rs2227981) had decreased odds for any grade treatment-related toxicities (n = 96; OR 0.4; 95% CI 0.2–1.0; p = 0.039). However, this result could not be validated (n = 85; OR 0.9; 95% CI 0.4–1.9; p = NS).
Conclusions: Our results show that it is unlikely that the investigated SNPs have a clinical implication in predicting toxicity. A finding, even though negative, that is considered timely and instructive towards further research in biomarker development for checkpoint inhibitor treatments.,
British Journal of Cancer
Department of Medical Oncology

Bins, S., Basak, E., El Bouazzaoui, S., Koolen, S., Oomen - de Hoop, E., van der Leest, C., … Mathijssen, R. (2018). Association between single-nucleotide polymorphisms and adverse events in nivolumab-treated non-small cell lung cancer patients. British Journal of Cancer, 1–6. doi:10.1038/s41416-018-0074-1