As reported in The Lancet Oncology by Fürstenau et al, 4-year follow-up of the phase III GAIA/CLL13 trial showed improved progression-free survival with venetoclax/obinutuzumab and venetoclax/obinutuzumab/ibrutinib vs both chemoimmunotherapy and venetoclax/rituximab in the first-line treatment of fit patients with chronic lymphocytic leukemia (CLL).
The primary analysis of the trial showed that venetoclax/obinutuzumab and venetoclax/obinutuzumab/ibrutinib improved undetectable measurable residual disease rates and progression-free survival compared with chemoimmunotherapy in this patient population.
Study Details
In the open-label trial, 926 patients from sites in 10 countries in Europe and the Middle East were randomly assigned 1:1:1:1 between December 2016 and October 2019 to receive chemoimmunotherapy (rituximab with either bendamustine or fludarabine/cyclophosphamide; n = 229), venetoclax/rituximab (n = 237), venetoclax/obinutuzumab (n = 229), or venetoclax/obinutuzumab/ibrutinib (n = 231). The primary outcome measure in the current analysis was investigator-assessed progression-free survival. The significance threshold for between-group comparisons was P = .025.
Key Findings
At data cutoff for the current analysis (end of January 2023), median follow-up was 50.7 months (interquartile range = 44.6–57.9 months). Progression-free survival was significantly better in the venetoclax/obinutuzumab group vs the chemoimmunotherapy group (hazard ratio [HR] = 0.47, 97.5% confidence interval [CI] = 0.32–0.69, P < .0001) and vs the venetoclax/rituximab group (HR = 0.57, 97.5% CI = 0.38–0.84, P = .0011).
Progression-free survival was also significantly better in the venetoclax/obinutuzumab/ibrutinib group vs the chemoimmunotherapy group (HR = 0.30, 97.5% CI = 0.19–0.47, P < .0001) and vs the venetoclax/rituximab group (HR = 0.38, 95% CI = 0.24–0.59, P < .0001).
The difference in progression-free survival between the venetoclax/obinutuzumab/ibrutinib group vs the venetoclax/obinutuzumab group did not reach the significance threshold (HR = 0.63, 97.5% CI = 0.39–1.02, P = .031). The proportional hazards assumption was not met for the comparison between the venetoclax/rituximab group vs the chemoimmunotherapy group (P = .10).
Progression-free survival at 4 years was 85.5% (97.5% CI = 79.9%–91.1%) in the venetoclax/obinutuzumab/ibrutinib group, 81.8% (97.5% CI = 75.8%–87.8%) in the venetoclax/obinutuzumab group, 70.1% (97.5% CI = 63.0%–77.3%) in the venetoclax/rituximab group, and 62.0% (97.5% CI = 54.4%–69.7%) in the chemoimmunotherapy group.
The investigators concluded, “With more than 4 years of follow-up, venetoclax/obinutuzumab and venetoclax/obinutuzumab/ibrutinib significantly extended progression-free survival compared with both chemoimmunotherapy and venetoclax/rituximab in previously untreated, fit patients with [CLL], thereby supporting their use and further evaluation in this patient group.”
Moritz Fürstenau, MD, of the German CLL Study Group, University of Cologne, Cologne, Germany, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by AbbVie, Janssen, and F. Hoffmann-La Roche. For full disclosures of the study authors, visit thelancet.com.
