The aim of this study was to evaluate the prognostic value of recurrent molecular abnormalities in patients with CLL. Therefore, we assessed their incidences and associations with other clinical and genetic markers in the prospective multicenter COMPLEMENT1 trial (treatment naive patients not eligible for intensive treatment randomized to chlorambucil (CHL) vs. ofatumumab-CHL (O-CHL))….for NOTCH1, we observed an impact on PFS in the O-CHL treatment arm (HR 1.94, 95%CI: 1.25-3.92, P<0.01) but not with CHL alone (HR 1.01, 95%CI: 0.69-1.47, P=0.98)...NOTCH1 as a predictive factor for reduced ofatumumab efficacy in a randomized chemo (immune)therapy CLL trial.