Comparing Venetoclax-Based Regimens, Chemoimmunotherapy in CLL

Treatment with venetoclax plus obinutuzumab with or without ibrutinib improved progression-free survival (PFS) compared with chemoimmunotherapy and venetoclax plus rituximab in treatment-naïve, fit patients with chronic lymphocytic leukemia (CLL), according to data from the GAIA/CLL13 trial published in The Lancet Oncology.

The lead author of this analysis, Moritz Fürstenau, MD, of the University of Cologne, added that measurable residual disease (MRD)-guided triplet therapy with “venetoclax-obinutuzumab-ibrutinib shows promising efficacy and yields longer PFS in patients with unmutated IGHV than the approved doublet of venetoclax-obinutuzumab, supporting a further evaluation of this approach.”

Between December 2016 and October 2019, the phase III GAIA/CLL13 study randomized 926 patients to receive either chemoimmunotherapy (n=229), venetoclax and rituximab (n=237), venetoclax and obinutuzumab (n=229), or venetoclax, obinutuzumab, and ibrutinib (n=231). The overall patient population had a mean age of 60.8 ± 10.2 years and was 72% male.

Best Venetoclax Combination for Treatment-Naïve CLL

With a median follow-up of 50.7 months (interquartile range, 44.6-57.9) in this exploratory analysis, patients who received venetoclax plus obinutuzumab had significantly longer PFS versus those who received chemoimmunotherapy (hazard ratio [HR], 0.47; 97.5% CI, 0.32-0.69; P<.0001) or venetoclax plus rituximab (HR, 0.57; 97.5% CI, 0.38-0.84; P=.0011).

Likewise, PFS was significantly longer with venetoclax plus obinutuzumab and ibrutinib compared with chemoimmunotherapy (HR, 0.30; 97.5% CI, 0.19-0.47; P<.0001) or venetoclax plus rituximab (HR, 0.38; 97.5% CI, 0.24-0.59; P<.0001).

Dr. Fürstenau and colleagues reported there was no difference in PFS between the venetoclax plus obinutuzumab and venetoclax plus obinutuzumab and ibrutinib groups (HR, 0.63; 97.5% CI, 0.39-1.02; P=.031).

The estimated rates of four-year PFS were as follows

• Venetoclax, obinutuzumab, and ibrutinib: 85.5% (97.5% CI, 79.9-91.1)
• Venetoclax and obinutuzumab: 81.8% (97.5% CI, 75.8-87.8)
• Venetoclax and rituximab: 70.1% (97.5% CI, 63.0-77.3)
• Chemoimmunotherapy: 62.0% (97.5% CI, 54.4-69.7)

“In summary, in patients with previously untreated CLL and a low burden of coexisting conditions, time-limited venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib improved PFS over venetoclax-rituximab and chemoimmunotherapy,” Dr. Fürstenau summarized.

Reference

Fürstenau M, Kater AP, Robrecht S, et al. First-line venetoclax combinations versus chemoimmunotherapy in fit patients with chronic lymphocytic leukaemia (GAIA/CLL13): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2024;25(6):744-759. doi:10.1016/S1470-2045(24)00196-7