Fixed-duration venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: Follow-up of efficacy and safety results from the multicenter, open-label, randomized phase 3 CLL14 trial.

Background: The CLL14 trial demonstrated significant improvement of progression-free survival (PFS) with fixed-duration venetoclax-obinutuzumab (VenG) as compared to chlorambucil-obinutuzumab (ClbG) in patients with previously untreated CLL and coexisting conditions. Aim(s): The aim of this report is to provide efficacy and safety data from follow-up of the CLL14 trial with now all patients being off treatment for at least 2 years. Method(s): Patients with previously untreated chronic lymphocytic leukaemia and coexisting conditions were randomized 1:1 to receive 12 cycles of venetoclax with 6 cycles of obinutuzumab or 12 cycles of chlorambucil with 6 cycles of obinutuzumab. Primary endpoint was investigator- assessed PFS. Key secondary endpoints were response rates, rates of minimal residual disease (measured every 6 months up to 5 years after last patient enrolment) and overall survival. Follow-up is ongoing but all patients are off study treatment. This trial was registered with ClinicalTrials.gov, number NCT02242942. Result(s): Of the 432 enrolled patients, 216 were randomly assigned to receive VenG and 216 to receive ClbG. After a median follow-up of 39.6 months (interquartile range 36.8 - 43.0), progression-free survival continued to be superior for VenG as compared to ClbG (median not reached vs 35.6 months; hazard ratio [HR] 0.31 [0.22-0.44], p<0.001)(Figure A). At 3 years, the estimated PFS rate was 81.9% in the VenG arm and 49.5% in the ClbG arm. This benefit was consistently observed across all clinical and biological risk groups, including patients with TP53 mutation/deletion and unmutated IGHV status. Of note, PFS was also significantly longer for VenG treated patients with mutated IGHV status compared to ClbG (HR 0.33 [0.16-0.70] p = 0.004). Overall, 21 disease progressions after VenG treatment have been observed. Assessment of minimal residual disease in peripheral blood 18 months after the end of treatment showed that 47.2% of patients in the VenG arm