Statistical analysis
malignancy, death, primary malignancies
REGRESSION, EVENTS, SECONDARY
The study sample size was calculated based on an assumed hazard ratio for progression or death of 0.65, with 170 events providing power of approximately 80% on the basis of a log-rank test stratified according to Binet stage and geographic region, with a two-sided statistical significance level of 0.05.This report presents an updated analysis of survival and MRD status, as well association between gene expression and MRD response. Kaplan–Meier estimates were used to analyse the time-to-event data of PFS, OS and TTNT. Comparisons were done by a two-sided log-rank test and Cox proportional hazards regression model (both stratified by Binet stage and geographic region). Time to second primary malignancies referred to the time between randomization and date of first diagnosis of secondary malignancy. It was evaluated by competing risk analysis considering death as a competing risk and was compared by two-sided Gray’s test for equality of cumulative incidence functions. Patients without reported death or secondary malignancy were censored at the date when they were last known to be alive.MRD response was defined as end of treatment MRD status <10Landmark analyses from last treatment exposure were performed for PFS as pre-planned and for OS as post-hoc regarding MRD level at end of treatment. Treatment arm and baseline characteristics (as listed in Supplementary Table All randomly assigned patients were included in the efficacy analyses (intention-to-treat population). All randomly assigned patients who received at least one dose of study medication (i.e., obinutuzumab, venetoclax, or chlorambucil) were included in the safety analyses (safety population).Analyses were performed using SPSS version 28 (SPSS, Chicago, IL, USA), SAS version 9.4 (SAS Institute, Cary, NS, USA) and R version 3.6.1 (R Foundation, Vienna, Austria). R packages limma, Seurat, DESeq2, fGSEA and GSVA were used for the transcriptomic analyses.