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.

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Persistent URL dx.doi.org/10.1038/s41416-018-0074-1, hdl.handle.net/1765/106144
Journal British Journal of Cancer
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Citation
Bins, S, Basak, E.A, El Bouazzaoui, S, Koolen, S.L.W, Oomen - de Hoop, E, van der Leest, K.H, … Mathijssen, A.H.J. (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