Dr Fürstenau on the Rationale for the GAIA/CLL13 Trial in Previously Untreated CLL

Moritz Fürstenau, MD, Division of Haematology, Immunology, Infectiology, Intensive Care, and Oncology, University of Cologne, discusses the rationale for launching the phase 3 GAIA/CLL13 trial (NCT02950051) investigating venetoclax (Venclexta) plus obinutuzumab (Gazyva) with or without ibrutinib (Imbruvica) vs chemoimmunotherapy in previously untreated, fit patients with chronic lymphocytic leukemia (CLL).

The rationale behind investigating venetoclax-based combinations in the GAIA trial was multifaceted, driven by existing evidence and the need for further comparative analyses in various patient populations, Fürstenau begins. The GAIA trial specifically examined 3 different time-limited venetoclax combinations.

One of these combinations, venetoclax plus obinutuzumab, has already received FDA approval for the first-line treatment of patients with CLL, he explains. Previous phase 2 and phase 3 trials demonstrated significant efficacy with this combination in certain patient subgroups, particularly older patients, Fürstenau says. Given these data, the GAIA trial evaluated whether this combination would also outperform the established standard regimen of fludarabine, cyclophosphamide, and rituximab (FCR) in the first-line setting in fit patients, he elucidates. This comparison is crucial because determining a superior alternative to FCR could significantly impact patient outcomes, Fürstenau reports.

The second combination investigated was venetoclax plus rituximab (Rituxan). The overall rationale for GAIA was to conduct a direct comparison between the 2 CD20-directed antibodies used in CLL management: obinutuzumab and rituximab, he continues. By evaluating the efficacy of venetoclax plus rituximab, the researchers determined whether rituximab could provide the same efficacy as obinutuzumab, Fürstenau notes, adding that this comparison is important for optimizing treatment protocols.

The third combination explored was a triplet regimen comprising venetoclax, obinutuzumab, and ibrutinib, he expands. This combination represented a logical progression in the effort to enhance treatment efficacy, according to Fürstenau. By adding ibrutinib to the already-potent venetoclax and obinutuzumab combination, the researchers assessed whether this triplet could offer superior efficacy, he emphasizes. Additionally, the trial evaluated the toxicity profile of this more intensive regimen, balancing its potential benefits against the risks to determine its suitability for broader clinical use, Fürstenau concludes.