Sensitivity of the cfDNA assay, distribution of targeted gene variants, and clinical patient courses. (A) cfDNA VAFs at the EOT and midtreatment (interim) time points compared with matched PBMCs controls, establishing the empirically supported sensitivity threshold of 10−3. Null values are omitted due to log-scale representation. (B) Distribution of ctDNA follow-up variants, with the 3 most frequently mutated genes collectively accounting for 47% (81/170) of all non-Ig ctDNA variants, each detected in multiple samples. (C) Patient-specific treatment courses and ctDNA dynamics are shown horizontally. Colored segments indicate first- to third-line treatments and beyond (blue, yellow, and red, respectively) and follow-up (gray). PET-CT responses are marked with symbols: CMR, PMR, SD, and progressive disease (PD). ctDNA negativity (<0.1% VAF, red cross) and ctDNA reappearance (≥0.1% VAF, vertical arrow) are indicated. Additional markers include undetectable ctDNA (asterisk), death (black cross), and being alive at study termination (horizontal arrow). SD, stable disease.
