Kaplan-Meier curves of TFS stratified by mutational statuses with 4-year survival estimates. (A) TP53 mutations were associated with inferior 4-year TFS; TP53-mutated (42.9% [95% CI, 9.8% to 73.4%]) vs TP53-WT patients (79.8% [95% CI, 69.7% to 86.8%]) (P = .011). (B) SF mutations conferred a poorer 4-year TFS; SF-mutated (40% [95% CI, 12.3% to 67%]) vs SF-WT (81.5% [95% CI, 71.4% to 88.3%]) (P = .00039). (C) Comparing TFS in patients with HMR with low molecular risk (LMR) at 4 years; HMR 41.2% (95% CI, 23.3% to 72.7%) vs LMR 84.6% (95% CI, 76.9% to 93.1%) (P < .0001). (D) Stratifying patients with HMR mutations in this study by treatment arm demonstrates no amelioration of the negative impact of HMR mutation with RUX treatment; patients with HMR on RUX had TFS at 4 years of 36.4% (95% CI, 26.2% to 46.6%) and on BAT 50% (29.1% to 67.7%) (P = .505 between these arms) as compared to those without these mutations (ie, LMR) had TFS at 4 years of 84.7% (95% CI, 71.6% to 92%) on RUX and of 90.6% (95% CI, 78.5% to 96%) on BAT (P = .101 between these arms). The log-rank test was used to compare survival estimates between groups. (E) Forest plot showing multivariable Cox model of TFS. Covariates significant on univariate analysis were included; TP53 mutations, SF mutations, treatment arm, JAK2V617F mutation status, disease duration at trial entry (TE), age, and sex. HMR mutations independently retained negative impact on TFS with a hazard ratio (HR) of 4.21 (P = .006). Treatment arm, JAK2V617F status, disease duration at TE, and age were not significant but, notably, male sex was associated with a poorer TFS (HR, 4.5; P = .006). Driver mutation allele ≥50% was independently associated with a poorer TFS (HR, 4.11; P = .016). Age and disease duration at TE were categorized as continuous variables. Significant P values on forest plot; *P < .05, **P < .01. HMR, high molecular risk (SF and TP53 mutations); JAK2, JAK2V617F; LMR, low molecular risk (without SF or TP53 mutations); SF, splicing factor mutation (SF3B1, ZRSR2, SRSF2).