Despite significant breakthroughs in targeted therapy for patients with high-risk chronic lymphocytic leukemia (CLL) [del(17p) and/or TP53 mutation], the result remained poor when compared to other patients with CLL. Combining different medicines with unique modes of action might boost outcomes even more. CLL2-GIVe was a multicenter, open-label experiment that included patients with previously untreated CLL who had del(17p) and/or TP53 mutations. Patients received obinutuzumab (GA-101), ibrutinib, venetoclax (GIVe) induction therapy for cycles 1–6, venetoclax, and ibrutinib consolidation therapy for cycles 7–12. In patients who did not achieve a complete response (CR) with serial undetectable minimum residual disease (uMRD) following consolidation, ibrutinib monotherapy was maintained for cycles 13 through 36. The primary goal was to determine the CR rate at cycle 15. (final restaging). MRD, survival, and safety were all secondary goals. Between September 2016 and August 2018, all 41 participants recruited in the trial received study therapy and were included in efficacy and safety populations. 

The main goal was reached with a CR rate of 58.5% at cycle 15 (95% CI: 42.1-73.7; P<.001). At the final restaging, 78.0% of patients had uMRD in their peripheral blood (PB), and 65.9% of patients had uMRD in their bone marrow (BM). At 24 months, the estimated progression-free survival (PFS) and overall survival (OS) rates were 95.1%. All patients documented adverse events, with the majority being of mild severity (grade >3: 23.9%). Two deaths were recorded (cardiac failure and ovarian cancer), neither of which was connected to study therapy.