Venetoclax Combinations Versus Chemoimmunotherapy in CLL

According to a study published in the New England Journal of Medicine, data on venetoclax combined with anti-CD20 antibodies as a first-line treatment in fit patients with advanced chronic lymphocytic leukemia (CLL) are sparse. Researchers led by Barbara Eichhorst, MD, conducted an open-label, phase III trial to compare chemoimmunotherapy with venetoclax plus either rituximab, obinutuzumab, or obinutuzumab and ibrutinib.

After analysis, Dr. Eichhorst and colleagues concluded venetoclax plus obinutuzumab with or without ibrutinib was superior to conventional chemoimmunotherapy as a first-line treatment in patients with CLL without TP53 mutations who are fit—defined as those with a low level of coexisting conditions.

Venetoclax Plus Obinutuzumab, but Not Rituximab, Improved CLL

The study enrolled 926 patients to receive either six cycles of chemoimmunotherapy (n=229) or 12 cycles of venetoclax plus rituximab (n=237), venetoclax plus obinutuzumab (n=229), or venetoclax plus obinutuzumab and ibrutinib (n=231). Ibrutinib could be halted or extended after two consecutive undetectable measurable residual disease (MRD) evaluations. The primary outcomes were undetectable MRD in peripheral blood on flow cytometry at month 15 and progression-free survival (PFS).

Notably, authors found the proportion of patients with undetectable MRD was significantly higher in the venetoclax plus obinutuzumab group at 86.5% (97.5% CI, 80.6-91.1) and the venetoclax plus obinutuzumab and ibrutinib group at 92.2% (97.5% CI, 87.3-95.7) compared with the chemoimmunotherapy group at 52.0% (97.5% CI, 44.4-59.5; P<.001). The proportion in the venetoclax plus rituximab group, 57.0% (97.5% CI, 49.5-64.2; P=.32), was not significantly different from chemoimmunotherapy.

Compared with the three-year PFS rate of 75.5% in the chemoimmunotherapy group, the venetoclax plus obinutuzumab and ibrutinib group had a rate of 90.5% (hazard ratio [HR] for progression or death, 0.32; 97.5% CI, 0.19-0.54; P<.001) and the venetoclax plus obinutuzumab group had a rate of 87.7% (HR, 0.42; 97.5% CI, 0.26-0.68; P<.001). The three-year PFS rate of 80.8% in the venetoclax plus rituximab group was again not significantly different from chemoimmunotherapy (HR, 0.79; 97.5% CI, 0.53-1.18; P=.18)

Ultimately, the study’s investigators concluded that “venetoclax-obinutuzumab with or without ibrutinib was superior to chemoimmunotherapy as [a] first-line treatment in fit patients with CLL.”

Reference

Eichhorst B, Niemann CU, Kater AP, et al. First-line venetoclax combinations in chronic lymphocytic leukemia. N Engl J Med. 2023;388(19):1739-1754. doi:10.1056/NEJMoa2213093