GAIA
Standard Chemoimmunotherapy (FCR/BR) Versus Rituximab + Venetoclax (RVe) Versus Obinutuzumab (GA101) + Venetoclax (GVe) Versus Obinutuzumab + Ibrutinib + Venetoclax (GIVe) in Fit Patients With Previously Untreated Chronic Lymphocytic Leukemia (CLL) Without Del(17p) or TP53 Mutation
Phase 3N = 926NCT02950051
- Population
- Fit patients (low burden of coexisting conditions) with previously untreated advanced CLL without TP53 aberrations.
- Design
- Open-label randomised phase 3, 1:1:1:1: six cycles of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) versus 12 cycles of venetoclax-rituximab, venetoclax-obinutuzumab, or venetoclax-obinutuzumab-ibrutinib (ibrutinib stopped after two consecutive undetectable MRD measurements, or extended). Coprimary endpoints: undetectable MRD in peripheral blood at month 15 and progression-free survival.
- Primary endpoint
- Undetectable MRD rate, PFS
- Arms
- Chemoimmunotherapy (control, n = 229): FCR or BR for six cycles
- Venetoclax-rituximab (experimental, n = 237): 12 cycles of venetoclax-rituximab
- Venetoclax-obinutuzumab (experimental, n = 229): 12 cycles of venetoclax-obinutuzumab
- Venetoclax-obinutuzumab-ibrutinib (experimental, n = 231): 12 cycles of venetoclax-obinutuzumab plus ibrutinib
- People
- Eichhorst B
Δ Undetectable MRD rate+5 pointsPFSHR 0.32Δ 36-month PFS+15 pointsPFSHR 0.42Δ 36-month PFS+12.2 pointsPFSHR 0.79
Show the numbers
| Endpoint | Analysis | Venetoclax-rituximab / Venetoclax-obinutuzumab / Venetoclax-obinutuzumab-ibrutinib | Chemoimmunotherapy | Effect |
|---|---|---|---|---|
| Undetectable MRD rateAll randomised patients (926)Undetectable MRD (below 1 CLL cell in 10,000 leukocytes) in peripheral blood at month 15 by flow cytometry | primaryEichhorst 2023 | 57% | 52% | P<0.001P<0.001 for venetoclax-obinutuzumab and for venetoclax-obinutuzumab-ibrutinib versus chemoimmunotherapy; P=0.32 for venetoclax-rituximab. The abstract gives 97.5% confidence intervals: chemoimmunotherapy 44.4 to 59.5, venetoclax-obinutuzumab 80.6 to 91.1, venetoclax-obinutuzumab-ibrutinib 87.3 to 95.7. Per the 4-year report, the coprimary comparison for this endpoint was venetoclax-obinutuzumab versus chemoimmunotherapy; the other comparisons are not coprimary. |
| PFSAll randomised patients (926) | primaryEichhorst 2023 | 90.5% at 3 y | 75.5% at 3 y | HR 0.32P<0.001Venetoclax-obinutuzumab-ibrutinib versus chemoimmunotherapy. The abstract gives a 97.5% confidence interval for the hazard ratio: 0.19 to 0.54. Per the 4-year report, this is the coprimary PFS comparison (investigator-assessed). |
| PFSAll randomised patients (926) | primaryEichhorst 2023 | 87.7% at 3 y | 75.5% at 3 y | HR 0.42P<0.001Venetoclax-obinutuzumab versus chemoimmunotherapy. The abstract gives a 97.5% confidence interval for the hazard ratio: 0.26 to 0.68. Not one of the two coprimary comparisons named in the 4-year report. |
| PFSAll randomised patients (926) | primaryEichhorst 2023 | 80.8% at 3 y | 75.5% at 3 y | HR 0.79P=0.18Venetoclax-rituximab versus chemoimmunotherapy: not significantly different in the abstract. The abstract gives a 97.5% confidence interval for the hazard ratio: 0.53 to 1.18. Not one of the two coprimary comparisons named in the 4-year report. |
| PFSAll randomised patients (926) | exploratorymedian follow-up 50.7 monthsFürstenau 2024 | 81.8% at 4 y | 62% at 4 y | HR 0.47P<0.0001Post-hoc exploratory analysis of updated PFS, data cutoff 31 January 2023, venetoclax-obinutuzumab versus chemoimmunotherapy. The abstract gives a 97.5% confidence interval for the hazard ratio: 0.32 to 0.69. 4-year 97.5% CIs: venetoclax-obinutuzumab 75.8 to 87.8, chemoimmunotherapy 54.4 to 69.7. |
| PFSAll randomised patients (926) | exploratorymedian follow-up 50.7 monthsFürstenau 2024 | 85.5% at 4 y | 62% at 4 y | HR 0.3P<0.0001Post-hoc exploratory analysis, venetoclax-obinutuzumab-ibrutinib versus chemoimmunotherapy. The abstract gives a 97.5% confidence interval for the hazard ratio: 0.19 to 0.47. 4-year 97.5% CIs: venetoclax-obinutuzumab-ibrutinib 79.9 to 91.1, chemoimmunotherapy 54.4 to 69.7. |
| PFSAll randomised patients (926) | exploratorymedian follow-up 50.7 monthsFürstenau 2024 | 70.1% at 4 y | 62% at 4 y | P=0.10Post-hoc exploratory analysis, venetoclax-rituximab versus chemoimmunotherapy. The abstract states that the proportional hazards assumption was not met for this comparison (log-rank p=0.10) and gives no hazard ratio. 4-year 97.5% CI for venetoclax-rituximab: 63.0 to 77.3. |
| PFSAll randomised patients (926) | exploratorymedian follow-up 50.7 monthsFürstenau 2024 | 70.1% at 4 y | — | HR 0.57P=0.0011Post-hoc exploratory head-to-head comparison, venetoclax-obinutuzumab versus venetoclax-rituximab. The abstract gives a 97.5% confidence interval for the hazard ratio: 0.38 to 0.84. |
| PFSAll randomised patients (926) | exploratorymedian follow-up 50.7 monthsFürstenau 2024 | 81.8% at 4 y | — | HR 0.63P=0.031Post-hoc exploratory head-to-head comparison, venetoclax-obinutuzumab-ibrutinib versus venetoclax-obinutuzumab; the abstract reports no difference in progression-free survival. The abstract gives a 97.5% confidence interval for the hazard ratio: 0.39 to 1.02. |
| Endpoint | Analysis | Venetoclax-rituximab / Venetoclax-obinutuzumab / Venetoclax-obinutuzumab-ibrutinib | Chemoimmunotherapy | Effect |
|---|---|---|---|---|
| Undetectable MRD rateAll randomised patients (926)Undetectable MRD (below 1 CLL cell in 10,000 leukocytes) in peripheral blood at month 15 by flow cytometry | primaryEichhorst 2023 | 57% | 52% | P<0.001P<0.001 for venetoclax-obinutuzumab and for venetoclax-obinutuzumab-ibrutinib versus chemoimmunotherapy; P=0.32 for venetoclax-rituximab. The abstract gives 97.5% confidence intervals: chemoimmunotherapy 44.4 to 59.5, venetoclax-obinutuzumab 80.6 to 91.1, venetoclax-obinutuzumab-ibrutinib 87.3 to 95.7. Per the 4-year report, the coprimary comparison for this endpoint was venetoclax-obinutuzumab versus chemoimmunotherapy; the other comparisons are not coprimary. |
| PFSAll randomised patients (926) | primaryEichhorst 2023 | 90.5% at 3 y | 75.5% at 3 y | HR 0.32P<0.001Venetoclax-obinutuzumab-ibrutinib versus chemoimmunotherapy. The abstract gives a 97.5% confidence interval for the hazard ratio: 0.19 to 0.54. Per the 4-year report, this is the coprimary PFS comparison (investigator-assessed). |
| PFSAll randomised patients (926) | primaryEichhorst 2023 | 87.7% at 3 y | 75.5% at 3 y | HR 0.42P<0.001Venetoclax-obinutuzumab versus chemoimmunotherapy. The abstract gives a 97.5% confidence interval for the hazard ratio: 0.26 to 0.68. Not one of the two coprimary comparisons named in the 4-year report. |
| PFSAll randomised patients (926) | primaryEichhorst 2023 | 80.8% at 3 y | 75.5% at 3 y | HR 0.79P=0.18Venetoclax-rituximab versus chemoimmunotherapy: not significantly different in the abstract. The abstract gives a 97.5% confidence interval for the hazard ratio: 0.53 to 1.18. Not one of the two coprimary comparisons named in the 4-year report. |
| PFSAll randomised patients (926) | exploratorymedian follow-up 50.7 monthsFürstenau 2024 | 81.8% at 4 y | 62% at 4 y | HR 0.47P<0.0001Post-hoc exploratory analysis of updated PFS, data cutoff 31 January 2023, venetoclax-obinutuzumab versus chemoimmunotherapy. The abstract gives a 97.5% confidence interval for the hazard ratio: 0.32 to 0.69. 4-year 97.5% CIs: venetoclax-obinutuzumab 75.8 to 87.8, chemoimmunotherapy 54.4 to 69.7. |
| PFSAll randomised patients (926) | exploratorymedian follow-up 50.7 monthsFürstenau 2024 | 85.5% at 4 y | 62% at 4 y | HR 0.3P<0.0001Post-hoc exploratory analysis, venetoclax-obinutuzumab-ibrutinib versus chemoimmunotherapy. The abstract gives a 97.5% confidence interval for the hazard ratio: 0.19 to 0.47. 4-year 97.5% CIs: venetoclax-obinutuzumab-ibrutinib 79.9 to 91.1, chemoimmunotherapy 54.4 to 69.7. |
| PFSAll randomised patients (926) | exploratorymedian follow-up 50.7 monthsFürstenau 2024 | 70.1% at 4 y | 62% at 4 y | P=0.10Post-hoc exploratory analysis, venetoclax-rituximab versus chemoimmunotherapy. The abstract states that the proportional hazards assumption was not met for this comparison (log-rank p=0.10) and gives no hazard ratio. 4-year 97.5% CI for venetoclax-rituximab: 63.0 to 77.3. |
| PFSAll randomised patients (926) | exploratorymedian follow-up 50.7 monthsFürstenau 2024 | 70.1% at 4 y | — | HR 0.57P=0.0011Post-hoc exploratory head-to-head comparison, venetoclax-obinutuzumab versus venetoclax-rituximab. The abstract gives a 97.5% confidence interval for the hazard ratio: 0.38 to 0.84. |
| PFSAll randomised patients (926) | exploratorymedian follow-up 50.7 monthsFürstenau 2024 | 81.8% at 4 y | — | HR 0.63P=0.031Post-hoc exploratory head-to-head comparison, venetoclax-obinutuzumab-ibrutinib versus venetoclax-obinutuzumab; the abstract reports no difference in progression-free survival. The abstract gives a 97.5% confidence interval for the hazard ratio: 0.39 to 1.02. |
Appears in
Sources
Eichhorst B, Niemann CU, Kater AP, Fürstenau M, von Tresckow J, Zhang C, et al. First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia. N Engl J Med. 2023;388(19):1739-1754.
Fürstenau M, Kater AP, Robrecht S, von Tresckow J, Zhang C, Gregor M, et al. First-line venetoclax combinations versus chemoimmunotherapy in fit patients with chronic lymphocytic leukaemia (GAIA/CLL13): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2024;25(6):744-759.