The combination of venetoclax and obinutuzumab provides promising survival and quality-of-life (QOL) results in patients with previously untreated chronic lymphocytic leukemia (CLL), according to findings from the phase III CLL14 study. Results from the study were recently published in Blood.
“This report confirms the long-term safety and efficacy of one-year fixed-duration [venetoclax plus obinutuzumab] in patients with previously untreated CLL,” wrote the investigators.
Patients enrolled in CLL14 had previously untreated CLL and coexisting conditions. A total of 216 patients were randomized to 12 cycles of venetoclax plus obinutuzumab, and an additional 216 received a chlorambucil-plus-obinutuzumab regimen. The two cohorts together had a median age of 77 years at data cutoff and a median observation time of 76.4 months.
The trial’s primary endpoint was progression-free survival (PFS) rate. The PFS rate at six years after randomization was 53.1% in the venetoclax-obinutuzumab arm and 21.7% in the chlorambucil-obinutuzumab arm. Median PFS was longer in the venetoclax-obinutuzumab arm than in the chlorambucil-obinutuzumab arm, at 76.2 months versus 36.4 months (hazard ratio [HR], 0.40; P<.0001), respectively.
In the venetoclax-obinutuzumab arm, investigators also identified chromosome 17p deletion, unmutated immunoglobulin heavy-chain variable region gene, and lymph nodes ≥5 cm as independent prognostic factors for shorter PFS.
For key secondary study endpoints, the venetoclax-obinutuzumab arm saw longer six-year time to next treatment, at 65.2% compared with 37.1% in the chlorambucil-obinutuzumab arm (HR, 0.44; P<.0001). The six-year overall survival rate was 78.7% in the venetoclax-obinutuzumab arm and 69.2% in the chlorambucil-obinutuzumab arm (HR, 0.69; P=.052).
Five years after treatment, 7.9% of the intention-to-treat population in the venetoclax-obinutuzumab arm had undetectable measurable residual disease compared with 1.9% of this population in the chlorambucil-obinutuzumab arm.
“End-of-treatment [measurable] residual disease status is associated with progression-free and overall survival,” the investigators noted.
The follow-up adjusted second primary malignancy incidence rates were 2.3 and 1.4 per thousand patient-months in the venetoclax-obinutuzumab and chlorambucil-obinutuzumab arms, respectively.
Regarding patient-reported outcomes, the median time to definitive deterioration in either global health status or QOL was 82.1 months in the venetoclax-obinutuzumab arm and 65.1 months in the chlorambucil-obinutuzumab arm (HR, 0.70).
Reference
Al-Sawaf O, Robrecht S, Zhang C, et al. Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the phase 3 CLL14 study. Blood. 2024. doi:10.1182/blood.2024024631