CLL13 / GAIA
In fit patients, one year of venetoclax plus obinutuzumab (with or without ibrutinib) clearly beat the old chemotherapy standard.
Co-primary endpoints: uMRD at month 15 (GIV 92.2%, GV 86.5%, RV 57.0%, CIT 52.0%) and PFS (GIV and GV superior to CIT; RV not). 5-year PFS: GIV 81.3%, GV 69.8%, RV 57.4%, CIT 50.7%; 5-year OS 91-95% in all arms. NEJM 2023; 5-year update 2025-26. Showed that venetoclax needs obinutuzumab rather than rituximab, and that adding ibrutinib improves PFS at the cost of more toxicity.
- 92.2 vs 86.5 out of 100 had no detectable disease on sensitive tests with GIV compared with GV; 5.7 more per 100.
- Roughly one extra person helped for every 18 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- Other groups: RV 57 of 100; Chemoimmunotherapy 52 of 100.
- 81.3 vs 69.8 out of 100 alive without the cancer growing at 5 years with GIV compared with GV; 11.5 more per 100.
- Roughly one extra person helped for every 9 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- Other groups: RV 57.4 of 100; Chemoimmunotherapy 50.7 of 100.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- These results apply to the people the trial enrolled: Fit, previously untreated CLL without del(17p)/TP53: chemoimmunotherapy (FCR/BR) vs venetoclax-rituximab vs venetoclax-obinutuzumab vs venetoclax-obinutuzumab-ibrutinib. People in a different situation may not see the same effect.
- The trial selected people by a biomarker (17p); the result should not be assumed for people whose cancer does not have it.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
926 participants enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Undetectable MRD at month 15 (blood)primary | GIV | — | 92.2% | — | — | link |
| GV | — | 86.5% | ||||
| RV | — | 57% | ||||
| Chemoimmunotherapy | — | 52% | ||||
| Progression-free survival at 5 years | GIV | — | 81.3% | — | — | — |
| GV | — | 69.8% | ||||
| RV | — | 57.4% | ||||
| Chemoimmunotherapy | — | 50.7% |
AMPLIFY delivered the first all-oral, fixed-duration doublet for front-line CLL and supported its approval, giving fit patients a way to avoid both chemotherapy and years of continuous BTK inhibitor. It does not settle whether a doublet or triplet is best, or how AV compares with venetoclax-obinutuzumab. Patients with TP53 aberration were excluded and still need different strategies.
CLL14 established the first chemotherapy-free, fixed-duration regimen for front-line CLL and made MRD-guided thinking mainstream in the disease. Patients get a year of treatment and then a treatment-free period rather than indefinite therapy. The choice today is between fixed-duration venetoclax combinations and continuous BTK inhibitors, with no proven survival difference.
Pages like this
not linked directly; found by shared links- TrialCLL14
Shares Venetoclax + obinutuzumab (12 months), Michael Hallek, CLL14: one year of venetoclax plus obinutuzumab instead of chemo-immunotherapy in older, less fit CLL patients, Obinutuzumab.
- TrialAMPLIFY
Shares IGHV mutational status, AMPLIFY: fixed-duration acalabrutinib plus venetoclax, with or without obinutuzumab, versus chemo-immunotherapy in fit CLL patients, Obinutuzumab, BTK (Bruton tyrosine kinase).
- TrialGLOW
Shares AMPLIFY: fixed-duration acalabrutinib plus venetoclax, with or without obinutuzumab, versus chemo-immunotherapy in fit CLL patients, Obinutuzumab, Ibrutinib, BTK (Bruton tyrosine kinase).
- TrialCAPTIVATE
Shares MRD-negative complete remission, Ibrutinib, BTK (Bruton tyrosine kinase), BCL-2.
- Key paperMURANO: two years of venetoclax plus rituximab versus chemo-immunotherapy in relapsed CLL
Shares CLL14: one year of venetoclax plus obinutuzumab instead of chemo-immunotherapy in older, less fit CLL patients, Rituximab, CD20, BCL-2.
- TrialCELESTIAL-TNCLL
Shares Obinutuzumab, BTK (Bruton tyrosine kinase), BCL-2, Venetoclax.
- PairingBTK inhibitor + venetoclax, fixed duration
Shares AMPLIFY: fixed-duration acalabrutinib plus venetoclax, with or without obinutuzumab, versus chemo-immunotherapy in fit CLL patients, Ibrutinib, BTK (Bruton tyrosine kinase), BCL-2.
- TrialELEVATE-TN
Shares Obinutuzumab, BTK (Bruton tyrosine kinase), CD20, Chronic lymphocytic leukaemia.