(HealthDay News) — Venetoclax plus obinutuzumab, with or without ibrutinib, produces better outcomes than chemoimmunotherapy as first-line treatment for fit patients with chronic lymphocytic leukemia (CLL), according to a study published in The New England Journal of Medicine.
The phase 3 study included 926 patients with CLL who did not have TP53 mutations. They were randomly assigned to receive 6 cycles of chemoimmunotherapy (bendamustine and rituximab or fludarabine, cyclophosphamide, and rituximab) or 12 cycles of various venetoclax combinations.
A total of 229 patients received chemoimmunotherapy, 237 received venetoclax and rituximab, 229 received venetoclax and obinutuzumab, and 231 received venetoclax plus obinutuzumab and ibrutinib.
One of the study’s primary endpoints was the percentage of patients with undetectable minimal residual disease (MRD) in the peripheral blood at month 15. The percentage of MRD-negative patients was not significantly different between the venetoclax-rituximab group and the chemoimmunotherapy group (57.0% and 52.0%, respectively; P =.32).
However, the proportion of patients who were MRD negative was significantly higher in the venetoclax-obinutuzumab group (86.5%) and the venetoclax-obinutuzumab-ibrutinib group (92.2%) than in the chemoimmunotherapy group (P <.001 for both comparisons).
The study’s second primary endpoint was progression-free survival (PFS). At a median follow-up of 38.8 months, PFS was better in the venetoclax-obinutuzumab-ibrutinib group than in the chemoimmunotherapy group (hazard ratio [HR], 0.32; 97.5% CI, 0.19-0.54; P <.001).
PFS was also better in the venetoclax-obinutuzumab group than in the chemoimmunotherapy group (HR, 0.42; 97.5% CI, 0.26-0.68; P <.001). There was no significant difference in PFS between the venetoclax-rituximab group and the chemoimmunotherapy group (HR, 0.79; 97.5% CI, 0.53-1.18; P =.18).
The overall survival rate at 3 years was similar across the groups, at 95.3% in the venetoclax-obinutuzumab-ibrutinib group, 96.3% in the venetoclax-obinutuzumab group, 96.5% in the venetoclax-rituximab group, and 95.0% in the chemoimmunotherapy group.
The most common grade 3-4 adverse events (AEs) across all 4 treatment groups were cytopenias and infections. The rate of serious AEs was 47.7% in the chemoimmunotherapy group, 40.1% in the venetoclax-rituximab group, 44.7% in the venetoclax-obinutuzumab group, and 50.2% in the venetoclax-obinutuzumab-ibrutinib group.
“Venetoclax-obinutuzumab with or without ibrutinib was superior to chemoimmunotherapy as first-line treatment in fit patients with CLL,” the researchers concluded.
This study was supported by grants from AbbVie, Janssen, and Roche, which provided some of the study drugs.
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