Obinutuzumab, Ibrutinib, and Venetoclax Combination Demonstrates Sustained Remissions Among Patients With High-Risk CLL

Final Analysis of the Phase 2 CLL2-GIVe Trial

According to findings from the final analysis of the phase 2 CLL2-GIVe trial published in Blood, the GIVe regimen consisting of obinutuzumab, ibrutinib, and venetoclax demonstrated promising sustained remission and a manageable safety profile among patients with high-risk chronic lymphocytic leukemia (CLL) with deletion 17p (del[17p]) and/or tumor protein p53 (TP53) mutations. 

Henriette Huber, MD, Klinik für Innere Medizin III, Universitätsklinikum Ulm, Ulm, Germany, and coauthors aimed to assess complete remission among this patient population as the primary endpoint for this study. 

In this open-label multicenter trial, a total of 41 patients with high-risk CLL with del(17p) and/or TP53 mutation who had never undergone previous treatment were enrolled. During induction, patients were administered 6 cycles of the GIVe regimen, with venetoclax and ibrutinib continuing up to cycle 12 as consolidation therapy. Among patients not achieving a complete response and with detectable minimal residual disease, ibrutinib was administered until cycle 15 or up until cycle 36. 

At cycle 15, the complete remission rate was achieved among 58.5% of patients (95% confidence interval [CI], 42.1 to 73.7; P < .001)). The 36-month progression-free survival and overall survival were 79.9% and 92.6%, respectively. The study authors noted that 6 patients continued maintenance with ibrutinib. 

In terms of safety and toxicity assessments, adverse events of particular concern included neutropenia (48.8%, grade ≥3) and infections (19.5%, grade ≥3). Between cycles 1 and 12, cardiovascular toxicity of grade 3 occurred as atrial fibrillation at a rate of 2.4%. Additionally, hypertension occurred at a rate of 4.9% between cycles 1 and 6. The likelihood of developing adverse events of any grade and grade ≥3 was highest at induction and decreased over time. Disease progression was detected in 7 patients between cycles 27 and 42. 

As endpoints were met, Dr Huber and coauthors concluded, “the CLL2-GIVe regimen is a promising fixed-duration, first-line treatment for patients with high-risk CLL with a manageable safety profile.”

Source: 

Huber H, Tausch E, Schneider C, et al. Final analysis of the CLL2-GIVe trial: obinutuzumab, ibrutinib, and venetoclax for untreated CLL with del(17p)/TP53mut. Blood. Published online: September 14, 2023. doi:10.1182/blood.2023020013