The CRISTALLO phase 3 trial showed that fixed-duration venetoclax-obinutuzumab significantly improved rates of undetectable minimal residual disease in peripheral blood at month 15 compared with chemoimmunotherapy (FCR/BR) in fit patients with untreated chronic lymphocytic leukemia. Although progression-free survival differences were not yet statistically significant due to short follow-up, the safety profile of VenO remained manageable with no clinical tumor lysis syndrome events reported.
Study
|
Open-label, international, multicenter, randomized phase 3 trial [CRISTALLO, NCT04285567] |
| Fit patients with untreated CLL without del(17p)/TP53 mutations |
| Fixed-duration venetoclax-obinutuzumab (VenO, n=80) versus fludarabine, cyclophosphamide, and rituximab or bendamustine-rituximab (FCR/BR) (n=86)
|
Efficacy
|
ORR: 88.8% (VenO) vs 79.1% (FCR/BR) |
| CR/CRi: 50.0% vs 32.6% |
| Undetectable MRD (uMRD) in peripheral blood at month 15: 81.3% vs 54.7% (P=0.0004) |
| uMRD in peripheral blood at end of treatment: 81.3% vs 60.5% (P=0.0053) |
| uMRD in bone marrow at end of treatment: 70.0% vs 38.4% (P<0.0001) |
| 2yr PFS: 95.7% vs 90.4% (HR 0.49 [0.2-1.3]; P=0.13)
|
Safety
|
Grade >=3 AEs: neutropenia (54.5% VenO vs 51.8% FCR/BR), thrombocytopenia (29.9% vs 12.9%), infections grade >=3 (26.0% vs 24.7%) |
| Serious AEs: 61.0% vs 49.4% |
| AEs leading to treatment withdrawal: 13.0% vs 18.8%
|
Blood. Published online 2026 March 2
http://doi.org/10.1182/blood.2025030630
Reviewed by Ulas D. Bayraktar, MD on Jun 15, 2026
