Final analysis of the CLL2-GIVe trial: obinutuzumab, ibrutinib, and venetoclax for untreated CLL with del(17p)/ TP53 mut

• Published in: Blood 2023-09, Vol.142 (11), p.961-972
• Main Authors: Huber, Henriette, Tausch, Eugen, Schneider, Christof, Edenhofer, Simone, von Tresckow, Julia, Robrecht, Sandra, Giza, Adam, Zhang, Can, Fürstenau, Moritz, Dreger, Peter, Ritgen, Matthias, Illmer, Thomas, Illert, Anna Lena, Dürig, Jan, Böttcher, Sebastian, Niemann, Carsten U., Kneba, Michael, Al-Sawaf, Othman, Kreuzer, Karl-Anton, Fink, Anna-Maria, Fischer, Kirsten, Döhner, Hartmut, Hallek, Michael, Eichhorst, Barbara, Stilgenbauer, Stephan
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.2023020013

The final analysis of the open-label, multicenter phase 2 CLL2-GIVe trial shows response and tolerability of the triple combination of obinutuzumab, ibrutinib, and venetoclax (GIVe regimen) in 41 previously untreated patients with high-risk chronic lymphocytic leukemia (CLL) with del(17p) and/or TP53 mutation. Induction consisted of 6 cycles of GIVe; venetoclax and ibrutinib were continued up to cycle 12 as consolidation. Ibrutinib was given until cycle 15 or up to cycle 36 in patients not achieving a complete response and with detectable minimal residual disease. The primary end point was the complete remission rate at cycle 15, which was achieved at 58.5% (95% CI, 42.1-73.7; P < .001). The last patient reached the end of the study in January 2022. After a median observation time of 38.4 months (range, 3.7-44.9), the 36-month progression-free survival was 79.9%, and the 36-month overall survival was 92.6%. Only 6 patients continued ibrutinib maintenance. Adverse events of concern were neutropenia (48.8%, grade ≥3) and infections (19.5%, grade ≥3). Cardiovascular toxicity grade 3 occurred as atrial fibrillation at a rate of 2.4% between cycles 1 and 12, as well as hypertension (4.9%) between cycles 1 and 6. The incidence of adverse events of any grade and grade ≥3 was highest during induction and decreased over time. Progressive disease was observed in 7 patients between cycles 27 and 42. In conclusion, the CLL2-GIVe regimen is a promising fixed-duration, first-line treatment for patients with high-risk CLL with a manageable safety profile.