An overview of the clonal evolution identified in this study. (A) The patterns of clonal evolution identified, with an example of 1 patient from each pattern. This includes patient 28 (no evolution), patient 26 (new clone emergence), patient 27 (clonal selection), and patient 32 (clonal replacement). Gene names represent mutated CLL-relevant genes found within the indicated subclone. A, B, C, and D represent a unique cluster of variants seen within a given subclone that distinguishes it from other subclones. Richter’s transformation patients account for 4/19 of those with no evolution, 3/11 with new clone emergence, and 1/5 with clonal selection. (B) A breakdown of the clonal evolution found within each treatment cohort. Each cohort is separated into patients who continued to respond to the given BTKi and those who relapsed during BTKi treatment. (C) A Fisher’s exact test comparing the presence or absence of evolving subclones containing CLL-driver mutations to the treatment outcome of all patients.