Somatic background of CH in the cfDNA is induced during therapy, and TP53-related CH is associated with hematologic adverse events and outcome. (A) Oncoprint of mutations detected in plasma cfDNA after 6 cycles of therapy. All variants supported by at least 1 duplex read. (B) Forest plot showing t test results for enrichment of VAF in different genes between BL and after 6 cycles of therapy in the cfDNA. The x-axis shows log10-transformed VAF enrichment (diamond) and its 95% confidence interval. Ambiguous variants supported by at least 1 duplex read included in the analysis. Most significant genes with nonsilent alterations and immunoglobulin segments are shown. (C) Box and dot plots showing the cumulative duration of grade 3-4 neutropenia and thrombocytopenia during follow-up in days (y-axis) according to PPM1D/TP53 mutation status in the PB/BM samples at BL. Patients with at least 180 days free from progression included. Nonreporter variants detected in BM/PB or cfDNA with VAF of >1% in PB/BM considered. (D) Forest plot of Cox proportional hazards model covariables, HRs, 95% CIs, and P values for multivariable model for OS with TP53 mutation status, PPM1D/TP53 CH status, and MIPI. FDR, false discovery rate; PD, progressive disease.