Noninvasive real-time monitoring of the DLBCL clonal evolution on plasma cfDNA. Sequential analysis of plasma cfDNA collected at presentation, upon treatment, and at the end of treatment. Disease response assessment by PET/CT is also shown at the corresponding time points. Representative patients are shown. Among nonresponding patients (ID13 [A] and ID12 [B]), baseline mutations remain detectable in plasma cfDNA. Among relapsing patients, baseline mutations cleared from plasma cfDNA and appeared again at the time of relapse (ID1 [C]) or persisted despite clinical remission (ID9 [D]). Color codes indicate different variants. Gene mutations selected by treatment are highlighted.