Venetoclax Plus Obinutuzumab Yield PFS Improvement in Untreated CLL, With or Without Ibrutinib

Patients with treatment-naïve chronic lymphocytic leukemia who were treated with venetoclax and obinutuzumab with or without ibrutinib experienced a progression-free survival benefit compared with standard chemoimmunotherapy.

Treatment with obinutuzumab (Gazyva) and venetoclax (Venclexta) plus or minus ibrutinib (Imbruvica) resulted in significantly improved progression-free survival (PFS) compared with standard chemoimmunotherapy in patients with treatment-naïve chronic lymphocytic leukemia, according to findings from an interim analysis of the phase 3 GAIA/CLL13 trial (NCT02950051).

Data that were presented at the 2022 European Hematologic Association Congress indicated that after a median follow up of 38.8 months, the median PFS was 52.0 months in the chemoimmunotherapy arm; 52.3 months in the venetoclax and rituximab (Rituxan; RV) arm; and was not reached among those treated with obinutuzumab and venetoclax with (GIV) or without (GV) ibrutinib. The 3-year PFS rates in each respective treatment arm were 75.5%, 80.8%, 90.5%, and 87.7%.

Additionally, the 3-year PFS rates in those with mutated IGHV were 96.0%, 93.6%, 87.0%, and 89.9% for the GIV; the GV; the RV; and the chemoimmunotherapy arms, respectively. Among those with IGHV unmutated disease, the corresponding 3-year PFS rates were 86.6%, 82.9%, 76.4%, and 65.5%.

A total of 920 patients were included in the 4-arm study and were randomized 1:1:1:1. A total of 229 patients were included in the chemoimmunotherapy arm, 237 were in the RV arm, 229 were in the GV arm, and 231 were in the GIV arm. Those who enrolled to the chemoimmunotherapy arm and were younger than 65 years received fludarabine, cyclophosphamide, and rituximab, and those older than 65 years received bendamustine and rituximab. Patients with a TP53 mutation or deletion 17p were not included in the study.

The study’s primary end point was minimal residual disease negativity in the peripheral blood and PFS in the GIV cohort compared with standard chemoimmunotherapy.

Investigators used a standard ramp-up dose of venetoclax from 20 mg at cycle 1 on days 22 to 28; 50 mg on days 1 through 1, 100 mg on days 8 through 14, 200 mg on days 15 to 21, and 400 mg on days 22 through 28 of cycle 2; and 400 mg on days 1 to 28 for cycles 3 to 12. In cycle 1, intravenous obinutuzumab was given at 1000 mg over 2 doses on day 1, cycle 1 and was subsequently administered as a single dose on day 1 of cycles 2 through 6. Ibrutinib at 420 mg daily was given for all cycles. Rituximab was given at a dose of 375 mg/m2 on day 0 of cycle 1 and 500 mg/m2 on day 1 of cycles 2 through 6.


Eichhorst B, Niemann C, Kater A, et al. Time-limited venetoclax-obinutuzumab +/- ibrutinib is superior to chemoimmunotherapy in frontline chronic lymphocytic leukemia (CLL): PFS co-primary endpoint of the randomized phase 3 GAIA/CLL13 trial. Presented at: 2022 European Hematologic Association Congress; June 9-17, 2022; Vienna, Austria. Abstract LB2365.