Venetoclax-obinutuzumab combo bests chemoimmunotherapy among chronic lymphocytic leukemia patients

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 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.

The key findings of this study were:

1. 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) .

2. 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.

3. In the venetoclax-obinutuzumab-ibrutinib group, three-year progression-free survival was 90.5%, compared to 75.5% in the chemoimmunotherapy group.

4. In contrast to venetoclax-rituximab, progression-free survival at 3 years was also improved with venetoclax-obinutuzumab.

5. 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