medwireNews: Changes in the plasma levels of cell-free (cf)DNA could be used to assess the risk for early death and hyperprogression in patients undergoing immune checkpoint inhibitor (ICI) therapy for advanced non-small-cell lung cancer (NSCLC), Italian researchers have found.
Samples taken from 171 patients were assessed using next-generation sequencing before (T1) and after 3 or 4 weeks of ICI therapy (T2), explain Laura Bonanno (Istituto Oncologico Veneto IOV IRCCS, Padova) and co-authors in the British Journal of Cancer.
Overall, 31 patients had early deaths and five patients experienced hyperprogressive disease with one patient experiencing both outcomes.
Both the absolute and relative difference in cfDNA quantity before and after treatment significantly predicted early death, while the relative change in maximum variant allele fraction was significantly associated with the risk for hyperprogression.
A cfDNA concentration of 22.7 ng/mL was defined as the “optimal” level at T2 for predicting early death or hyperprogression with 81% accuracy, so that patients with higher values were 22.1 times more likely to experience either outcome, the researchers say.
Similarly, an absolute plasma cfDNA increase from baseline of 3.8 ng/mL or a relative increase of 0.2 ng/mL were significantly associated with corresponding 68.2- and 17.2-fold increases in the risk for early death or hyperprogression.
Bonanno et al emphasize the need for confirmatory research, but they suggest that their study “represents a proof-of-concept analysis concerning an innovative approach to the issue of predictive biomarkers of immunotherapy in lung cancer, focusing on patients who do not derive any clinical benefit and could benefit [from] a customised approach including early changes in treatment.”
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