Extended follow-up suggests that venetoclax plus obinutuzumab prolongs progression-free survival (PFS), but not overall survival (OS), when compared with chlorambucil plus obinutuzumab in patients with previously untreated chronic lymphocytic leukemia (CLL).
These results, from the CLL14 study (ClinicalTrials.gov Identifier: NCT02242942), were presented at the European Hematology Association (EHA) 2021 Virtual Congress.
The study enrolled 432 patients who were randomly assigned at a 1:1 ratio to receive venetoclax plus obinutuzumab or chlorambucil plus obinutuzumab. In each arm, patients received 6 cycles of the assigned combination, followed by 6 cycles of either venetoclax or chlorambucil alone.
The baseline characteristics was similar between the treatment arms. The median age was 72 years in the venetoclax arm and 71 years in the chlorambucil arm. Roughly 60% of patients had unmutated IGHV, and 12% had TP53 aberrations.
At a median follow-up of 52.4 months, the PFS was superior for venetoclax plus obinutuzumab (hazard ratio [HR], 0.33; 95% CI, 0.25-0.45; P <.0001). The median PFS was not reached in the venetoclax arm and was 36.4 months in the chlorambucil arm. The 4-year PFS rate was 74.0% and 35.4%, respectively.
For patients with TP53 aberrations, the median PFS was 49.0 months in the venetoclax arm and 20.8 months in the chlorambucil arm. For patients with unmutated IGHV, the median PFS was 57.3 months and 26.9 months, respectively.
The median time to next treatment was not reached in either arm. The 4-year time-to-next-treatment rate was 81.1% in the venetoclax arm and 59.9% in the chlorambucil arm (HR, 0.46; 95% CI, 0.32-0.65; P <.0001).
An analysis of minimal residual disease (MRD) status showed a longer duration of MRD negativity in patients treated with venetoclax plus obinutuzumab. The median time to MRD conversion was 21 months in the venetoclax arm and 6 months in the chlorambucil arm.
There was no significant difference in OS between the treatment arms. The median OS was not reached in either arm. The 4-year OS rate was 85.3% in the venetoclax arm and 83.1% in the chlorambucil arm (HR, 0.85; 95% CI, 0.54-1.35; P =.49).
Second primary malignancies were seen in 40 patients in the venetoclax arm and 30 in the chlorambucil arm. There were no new safety signals identified with extended follow-up.
Disclosures: This research was supported by Hoffmann-La Roche, AbbVie, and the German CLL Study Group. The presenter disclosed affiliations with Roche, Janssen, Gilead, AbbVie, AstraZeneca, BeiGene, and Adaptive Biotechnologies.
Al-Sawaf O, Zhang C, Robrecht S, et al. Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 4-year follow-up analysis of the randomized CLL14 study. Paper presented at: European Hematology Association 2021 Virtual Congress; June 2021; Abstract S146.