Triplet Therapy with ‘GIVe’ Shows Promising Results in High-Risk CLL Trial

Among patients with high-risk chronic lymphocytic leukemia (CLL) with deletion of chromosome 17p [del(17p)], TP53 mutation, or both, the triplet “GIVe regimen” of obinutuzumab, ibrutinib, and venetoclax was “a promising fixed-duration, first-line treatment,” based on the multicenter phase II CLL2-GIVe trial.

Lead author of the study, Henrietta Huber, MD, of Ulm University Hospital in Germany, and investigators reported the triplet therapy produced high rates of negative measurable residual disease (MRD) with durable responses.

The open-label phase II study enrolled 41 treatment-naïve patients to receive six cycles of GIVe as induction therapy, followed by up to 12 cycles of venetoclax and ibrutinib as consolidation therapy. Ibrutinib was administered up to 15 cycles in responders or up to 36 cycles in patients with no complete response and detectable MRD.  The primary endpoint was the rate of complete remission at cycle 15.

Favorable Treatment Outcomes with Obinutuzumab, Ibrutinib, and Venetoclax

A total of 58.5% of participants achieved the primary endpoint (95% CI, 42.1-73.7; P<.001). Additionally, over a median observation period of 38.4 months (range, 3.7-44.9), the 36-month rates of progression-free survival and overall survival were 79.9% and 92.6%, respectively. Authors noted six patients required continual ibrutinib maintenance therapy, while seven patients experienced disease progression between cycles 27 and 42.

Grade III or higher adverse events (AEs) included neutropenia in 48.8% of patients and infections in 19.5%. Any grade and grade III or higher AEs occurred most frequently during induction therapy and decreased over time.

In short, “time-limited triple therapy leads to high rates of undetectable [MRD] and sustained remissions in high-risk CLL,” Dr. Huber wrote.

Reference

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. 2023;142(11):961-972. doi:10.1182/blood.2023020013