Combination of Obinutuzumab, Ibrutinib, and Venetoclax for Untreated High-Risk CLL

By: Vanessa A. Carter, BS
Posted: Tuesday, April 19, 2022

The CLL-GIVe trial, conducted by Stephan Stilgenbauer, MD, of the University of Ulm, Germany, and colleagues, assessed the combination regimen of the monoclonal antibody obinutuzumab, the tyrosine kinase inhibitor ibrutinib, and the BCL2 inhibitor venetoclax in patients with chronic lymphocytic leukemia (CLL). The results of this study demonstrated that this regimen has a manageable safety profile with efficacy in patients with high-risk disease. These findings were published in the journal Blood.

“Our results indicate that the CLL2-GIVe regimen is a promising fixed-duration, first-line treatment for patients with TP53-aberrant CLL,” concluded the investigators. “These data provide a rationale to explore this triplet combination not only in high-risk CLL, where the unmet medical need is greatest, but also among all patients with untreated CLL as currently being evaluated within the CLL13/GAIA trial.”

This open-label, multicenter trial enrolled 41 patients with previously untreated CLL who had a 17p deletion and/or TP53 mutation. Participants received induction therapy with obinutuzumab, ibrutinib, and venetoclax for six cycles, and consolidation therapy with ibrutinib and venetoclax for six more cycles. Ibrutinib monotherapy was administered for cycles 13 through 36 for individuals who did not reach a complete response with undetectable measurable residual disease (MRD).

The median patient age was 62, and 24 patients had both a 17p deletion and a TP53 aberration; 15 participants had a TP53 mutation alone and 2 had a 17p deletion alone. The complete response rate was 58.5% (P < .001). Upon final restaging, many individuals had undetectable MRD in peripheral blood (78.0%) and bone marrow (65.9%). Interestingly, the estimated progression-free survival and overall survival rates were both 95.1% at 24 months.

Adverse events were reported in all patients, although most were lower than grade 3. Dose adjustments due to adverse events occurred in 31 patients, with 4.7% of events leading to dose reductions and 13.8% influencing dose interruptions. Two deaths from ovarian carcinoma and cardiac failure were reported, but neither were deemed related to the study treatment.

Disclosure: For full disclosures of the study authors, visit ashpublications.org.

Blood