GAIA/CLL13: Positive 5-year efficacy outcomes for GIV in CLL

The triple combination of venetoclax, ibrutinib, and obinutuzumab outperformed venetoclax plus obinutuzumab in terms of progression-free survival (PFS) in patients with previously untreated chronic lymphocytic leukaemia (CLL). However, after 5 years of follow-up, the researchers did not observe a difference between the treatment groups regarding overall survival (OS).

The phase 3 GAIA/CLL13 trial randomised 926 fit patients with newly diagnosed CLL 1:1:1:1 to venetoclax plus rituximab (RV), venetoclax plus obinutuzumab (GV), venetoclax plus obinutuzumab and ibrutinib (GIV), or chemoimmunotherapy (CIT) [1].

After a median follow-up duration of 63.8 months, the PFS of patients on GIV was superior to that of patients on GV (HR 0.61; 97.5% CI 0.41–0.91), RV (HR 0.35; 97.5% CI 0.24–0.51), or CIT (HR 0.34; 97.5% CI 0.24–0.50). The corresponding estimated 5-year PFS rates were 81.3% (GIV), 69.8% (GV), 57.4% (RV), and 50.7% (CIT). “We observed that the 5-year PFS rates were particularly different between treatment arms in the subgroup of participants with unmutated IGHV,” added Dr Arnon Kater (Amsterdam UMC, the Netherlands). Next, the 5-year OS rates were 94.3%, 93.6%, 94.7%, and 90.7%, respectively, displaying no significant difference between the treatment groups.

Fatal adverse events were observed in 59 participants, with 18 events in the CIT arm and 13 or 14 events in each of the other study arms. These deaths could mostly be adjudicated to Richter’s transformation (n=10), COVID-19 (n=6), or pneumonia (n=5).

“Although GIV prolongs PFS compared with the widely used standard-of-care GV in this population of patients with CLL, we need to consider tolerability, quality-of-life, and OS when we want to choose between GIV and GV,” decided Dr Kater.

1. Furstenau M, et al. The triple combination of venetoclax-ibrutinib-obinutuzumab prolongs progression-free survival compared to venetoclax-CD20-antibody combinations and chemoimmunotherapy in treatment-naïve chronic lymphocytic leukemia: final analysis from the phase 3 GAIA/CLL13 trial. S191, EHA2025 Congress, 12–15 June, Milan, Italy.

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Posted on 2 September 2025