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. 2024 Feb 22;14(6):1048–1063. doi: 10.1158/2159-8290.CD-23-1060

Figure 3.

Figure 3. Association of CSM and CMC with survival outcomes in patients with advanced cancer treated with pembrolizumab. Circulating tumor DNA was quantified using a methylation-based approach (CSM) and a bespoke tumor-informed mutation sequencing approach (CMC). A, Methylation probabilities were summed across 200 cancer-specific sites, curated based on independent analysis of methylation array data from The Cancer Genome Atlas. ΔCSM was calculated based on the change in CSM from SB to C3B. Changing regions are shown in the heat map, alongside final ΔCSM values. B, Decrease in CSM and CMC from baseline to cycle 3 are each associated with improved OS and PFS. C, In multivariable Cox analyses, ΔCSM was a significant, independent predictor of PFS and OS, adjusted for cohort, PD-L1 expression, and tumor mutation burden. D, A decrease in either CSM or CMC was associated with improved survival, whereas increase in both metrics identified patients with particularly poor outcome.

Association of CSM and CMC with survival outcomes in patients with advanced cancer treated with pembrolizumab. Circulating tumor DNA was quantified using a methylation-based approach (CSM) and a bespoke tumor-informed mutation sequencing approach (CMC). A, Methylation probabilities were summed across 200 cancer-specific sites, curated based on independent analysis of methylation array data from The Cancer Genome Atlas. ΔCSM was calculated based on the change in CSM from SB to C3B. Changing regions are shown in the heat map, alongside final ΔCSM values. B, Decrease in CSM and CMC from baseline to cycle 3 are each associated with improved OS and PFS. C, In multivariable Cox analyses, ΔCSM was a significant, independent predictor of PFS and OS, adjusted for cohort, PD-L1 expression, and tumor mutation burden. D, A decrease in either CSM or CMC was associated with improved survival, whereas increase in both metrics identified patients with particularly poor outcome.