BTK gatekeeper and alternate-site mutation selected during pirtobrutinib therapy for CLL. (A-F) Subclonal structure and clonal evolution of somatic mutations for 2 patients with CLL (CLL Pt 6 and CLL Pt 7) that progressed on pirtobrutinib derived using PhylogicNDT and Concerti. (A,D) Clonal evolution of somatic mutations derived using PhylogicNDT for 2 patients (CLL Pt 6 and CLL Pt 7). Each line represents the CCF distribution dynamics of mutation clusters, generated using the PhylogicNDT Cluster tool, at different time points. Shading represents the 95% confidence interval. (B,E) Phylogenetic tree (built by the PhylogicNDT BuildTree tool) represents the clonal and subclonal architecture. (C,F) Time-scaled Concerti fish plot and tumor evolution tree where width of the fish plot corresponds to absolute lymphocyte counts for the 2 patients (CLL Pt 6 and CLL Pt 7). Clones are sized proportionally to their prevalence and the tree is aligned by sample time point. Subclones are matched in color across the panels for each patient. Speb, spebrutinib; Ven, venetoclax.