Study flowchart and baseline clinical characteristics of CLL patients. (A) Study flowchart. Of 23 eligible patients with CLL, 18 had adequate circulating cells for RNA sequencing and RPPA. All 18 experienced partial remission while receiving pirtobrutinib. (B) Mutation status at baseline. BTK and PLCG2 mutations were identified using targeted next-generation sequencing. (C) The LDH levels in peripheral blood samples (left) and log-transformed lactate dehydrogenase A (LDHA) transcript levels in patients with WT and mutated BTK (right) are shown. (D) Showing the lymph node size in the 18 patients. To obtain the lymph node sizes, electronic medical records were reviewed, and the sum of the products of the diameter was plotted. For statistical evaluation, Welch’s unpaired, 1-tailed t test was used. (E) OncoPrint data demonstrating the baseline clinical features and genomic alterations of patients with BTK-WT or -mutated CLL. The data were obtained from patients’ medical records. All patients received treatment at MD Anderson as part of the multicenter BRUIN trial and previously received cBTKi-based therapy. Data in panels C-E were obtained from patients’ electronic medical records before initiation of treatment with pirtobrutinib. In addition, the data in panel C were obtained using a human ProcartaPlex Human Cytokine/Chemokine/Growth Factor Panel 1 cytokine assay kit using plasma samples obtained at baseline. P values for comparisons by BTK mutation status were determined using Welch’s unpaired, 1-tailed t test. MDACC, MD Anderson Cancer Center; monoRx, monotherapy; pirto, pirtobrutinib; R/R, relapsed/resistant.