Treatment effect in PFS according to MRD-negative rates. (A) The weighted trial-level R² (95% CI) observed in the aggregated analysis of the 15 clinical trials. PFS hazard ratio (HR) and MRD odds ratio (OR) values were natural log transformed. Circle size is proportional to the number of patients included in the study. (B) Clinical trials stratified according to the median difference of MRD-negative rate differences observed between experimental vs control arms, and corresponding median (p25-p75) difference in median PFS. Trials with differences in MRD-negative rates <12.3%: APOLLO, BOSTON, CLARION, DETERMINATION, and IFM 2009. Trials with differences in MRD-negative rates ≥12.3%: ALCYONE, ATLAS, CANDOR, CASTOR, MAIA, and POLLUX. P value for the comparison of median PFS improvement between trials with differences in MRD-negative rates <12.3% vs ≥12.3%: 0.074. The median PFS was not available for 1 or more intervention groups of the following trials: CASSIOPEIA, GEM2012MENOS65, GRIFFIN, and IKEMA; therefore, these trials were not included in this analysis. (C) Difference in MRD-negative rates between experimental vs control arms in clinical trials demonstrating with an HR lower vs equal or greater than 0.60 (supplemental Table 3). Trials with a HR ≥0.60: APOLLO, BOSTON, CLARION, DETERMINATION, GEM2012MENOS65, and IFM 2009. Trials with a HR <0.60: ALCYONE, CANDOR, CASSIOPEIA, CASTOR, GRIFFIN, IKEMA, MAIA and POLLUX.