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AACR 2024 | Ultra-sensitive ctDNA monitoring predicts ICI response in melanoma

Christoffer Gebhardt, MD, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, discusses findings from a retrospective study, which analyzed plasma samples from patients with advanced metastatic melanoma undergoing immune checkpoint inhibitor (ICI) treatment, such as nivolumab and ipilimumab. An increase in early circulating tumor DNA (ctDNA) predicted progression-free survival (PFS), while ctDNA clearance correlated with complete responses (CR). Molecular progression was a significant predictor of overall survival (OS), emphasizing the utility of ultra-sensitive ctDNA monitoring in late-stage melanoma for predicting ICI response. This interview took place at American Association for Cancer Research (AACR) Annual Meeting 2024 in San Diego, CA.

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Transcript (edited for clarity)

So it’s a project in collaboration with Personalis, a California based biotech company that developed an ultra sensitive ctDNA analysis platform, and with that technology, we actually analyzed a patient cohort derived from our center of advanced first line melanoma patients, metastatic melanoma patients that received checkpoint inhibitors, mainly nivo/ipi combination and with a biobanking and a sampling of every 3 to 4 weeks during treatment...

So it’s a project in collaboration with Personalis, a California based biotech company that developed an ultra sensitive ctDNA analysis platform, and with that technology, we actually analyzed a patient cohort derived from our center of advanced first line melanoma patients, metastatic melanoma patients that received checkpoint inhibitors, mainly nivo/ipi combination and with a biobanking and a sampling of every 3 to 4 weeks during treatment. We have a quite granular view on the ctDNA dynamics. This platform is unique in the sense that it is ultra sensitive, meaning it reaches a sensitivity down to one ppm, down to one parts per million, which is just 100 fold lower than, uh, than the sensitivity reached with the standard routine ctDNA measurement. The digital droplet PCR, which reaches 100 ppm per round. So with such an ultra sensitive approach, we were able actually to detect one third more into our cohort of patients with ctDNA levels and get informative information regarding the development of resistance, the development of a deep of a complete response even and therefore significantly associate these patients ctDNA dynamics with the clinical outcome.

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