ctDNA mutational load points to checkpoint inhibition outcomes
medwireNews: The mutational burden of circulating tumor (ct)DNA is an indicator of response to checkpoint inhibition-based cancer immunotherapy, with high loads linked to favorable outcomes, report researchers.
They explain that tumor mutational load is known to correlate with immunotherapy response, but the studies so far have used biopsy samples to assess the mutational status. The study authors therefore investigated the utility of blood-derived ctDNA to evaluate the burden of mutations, noting that the noninvasive and inexpensive nature of a liquid biopsy may make their findings “clinically exploitable.”
The study included 69 patients with solid malignancies – most commonly melanoma, lung cancer, and head and neck cancer – who received checkpoint inhibitor therapy between 2011 and 2016. ctDNA extracted from blood samples, obtained for the most part prior to the initiation of immunotherapy, underwent next-generation sequencing to identify alterations – both previously characterized and those of unknown significance – in 54–70 cancer-related genes.
Median progression-free survival (PFS) was significantly longer for the 29% of participants with ctDNA harboring more than the average of 3 variants of unknown significance than for the 71% with 3 or fewer variants of unknown significance, at 3.84 and 2.07 months, respectively (hazard ratio [HR]=0.52). This was also the case for overall survival (OS), with corresponding median times not reached and 10.72 months (HR=0.39).
Among the 66 participants with an evaluable response, those with more than versus three or fewer variants of unknown significance were more likely to have a response, defined as a complete or partial response or stable disease for at least 6 months, at rates of 45% versus 15%.
The findings were similar when mutational burden was defined on the basis of previously characterized variants and those of unknown significance, with the average of 6 alterations specifying the cutoff.
Lead author Yulian Khagi and colleagues, from the University of California San Diego Moores Cancer Center in La Jolla, USA, write in Clinical Cancer Research: “These data provide the impetus to further investigate liquid biopsy as a viable, noninvasive, predictive biomarker for checkpoint inhibitor response across various histologies.”
They emphasize, however, that the results need to be verified in larger, prospective studies in the future.
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