IPS-E stratified time to first treatment in early stage CLL patients managed with active surveillance. (A) Kaplan-Meier curves of TTFT stratified by IPS-E in the University of Eastern Piedmont discovery cohort. (B) Meta-analytic estimate of TTFT by IPS-E and the corresponding variability across the 9 Binet A validation cohorts. The bold line shows the cubic spline fitted on the meta-analytic estimate of the cumulative proportion of TTFT at each timepoint. The shadow shows the cubic splines fitted on the meta-analytic estimate of the 95% confidence interval of the cumulative proportion of TTFT at each timepoint. (C) Kaplan-Meier curves of time to first treatment stratified by IPS-E in the Mayo Clinic validation cohort. Blue, low-risk; green, intermediate-risk; red, high-risk by IPS-E. Multiplicity corrected P values by pairwise log-rank tests are shown. See Figure 2 in the article by Condoluci et al that begins on page 1859.