Venetoclax-Obinutuzumab Study in Chronic Lymphocytic Leukemia (CLL)

In healthy people with chronic lymphocytic leukemia (CLL), venetoclax-obinutuzumab with or without ibrutinib was better than chemoimmunotherapy, says an article published in the New England Journal of Medicine.

There aren't many randomized studies using venetoclax combined with anti-CD20 antibodies as first-line therapy for healthy individuals with advanced chronic lymphocytic leukemia (CLL) (i.e., those with a low burden of comorbid illnesses). Therefore, in order to evaluate venetoclax's effectiveness, Barbara Eichhorst and colleagues carried out this investigation.

Fit CLL patients without TP53 aberrations were randomly assigned, in a 1:1:1:1 ratio, to receive six cycles of fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab immunotherapy, or 12 cycles of venetoclax-rituximab, venetoclax-obinutuzumab, or venetoclax-obinutuzumab-ibrutinib. After two measures with undetectable minimum residual disease or the potential for an extension, ibrutinib was stopped. The main outcomes were progression-free survival and undetectable minimum residual disease (sensitivity, 10⁴ [i.e., 1 CLL cell in 10,000 leukocytes]), both measured by flow cytometry in peripheral blood at month 15.

Key Findings

• One of the four treatment plans was given to a total of 926 patients (229 to chemoimmunotherapy, 237 to venetoclax–rituximab, 229 to venetoclax–obinutuzumab, and 231 to venetoclax–obinutuzumab–ibrutinib).
• At month 15, the proportion of patients in the venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib groups was considerably greater than it was in the chemoimmunotherapy group, but it was not significantly higher in the venetoclax-rituximab group.
• In the venetoclax-obinutuzumab-ibrutinib group, three-year progression-free survival was 90.5%, compared to 75.5% in the chemoimmunotherapy group.
• In contrast to venetoclax-rituximab, progression-free survival at 3 years was also improved with venetoclax-obinutuzumab.
• Chemoimmunotherapy (18.5%) and venetoclax-obinutuzumab-ibrutinib (21.2%) caused higher grade 3 and grade 4 infections than venetoclax-rituximab (10.5%) or venetoclax-obinutuzumab (13.2%).

Source

Eichhorst, B., Niemann, C. U., Kater, A. P., Fürstenau, M., von Tresckow, J., Zhang, C., Robrecht, S., Gregor, M., Juliusson, G., Thornton, P., Staber, P. B., Tadmor, T., Lindström, V., Nösslinger, T., … Hallek, M. (2023). First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia. In New England Journal of Medicine (Vol. 388, Issue 19, pp. 1739–1754). Massachusetts Medical Society. https://doi.org/10.1056/nejmoa2213093