This phase 3 trial in untreated chronic lymphocytic leukemia patients showed that fixed-duration treatment with venetoclax combinations was noninferior to continuous ibrutinib in progression-free survival. Fixed-duration regimens achieved higher rates of undetectable minimal residual disease and complete response compared to ibrutinib. Safety profiles differed, with more serious adverse events and infusion reactions observed in the venetoclax–obinutuzumab group, while infection-related deaths were more frequent in the fixed-duration venetoclax–obinutuzumab arm.
Study
|
Phase 3, randomized, international, investigator-initiated trial [CLL17] |
| Previously untreated chronic lymphocytic leukemia |
| Fixed-duration venetoclax (x12 cycles) – obinutuzumab (x6 cycles) (n=303) vs fixed-duration venetoclax (x12 cycles) – ibrutinib (x15 cycles) (n=305) vs continuous ibrutinib (n=301)
|
Efficacy
|
CR: 51.5% vs 46.2% vs 8.3% (venetoclax-obinutuzumab vs. venetoclax-ibrutinib vs. continuous ibrutinib) (P<0.0001 both vs ibrutinib) |
| 3yr-PFS: 81.1% vs 79.4% vs 81.0% (HR 0.87 [0.54-1.41] and 0.84 [0.53-1.32] vs ibrutinib) |
| Undetectable MRD in peripheral blood at therapy end: 73.3% vs 47.2% vs 0% (P<0.0001 for both fixed-duration regimens vs ibrutinib) |
| Undetectable MRD in bone marrow at restaging: 62.0% vs 40.0% vs 0% (P<0.0001 for both fixed-duration regimens vs ibrutinib) |
| 3yr-OS: 91.5% vs 96.0% vs 95.7% |
| In patients with del(17p) or TP53 mutation: 3yr-PFS: 62.0% vs 69.0% vs 79.4% |
| In patients with complex karyotype: 3yr-PFS: 62.2% vs 82.3% vs 80.1%
|
Safety
|
Grade >=3 adverse events: Covid-19 infections (15.9% vs 8.6% vs 6.7%), tumor lysis syndrome (3.3% vs 1.3% vs 0.3%), infusion-related reactions (39.7% [grades 3-4: 11.2%] vs not reported vs not reported), cardiac disorders (13.9% vs 23.8% vs 34.6%), second primary cancer (11.9% vs 11.6% vs 18.5%), Richter transformation (1.3% vs 0.3% vs 1.3%), treatment discontinuation due to adverse events (14.6% vs 22.1% vs 33.2%)
|
N Engl J Med 2026;394:1084-96
http://doi.org/10.1056/NEJMoa2515458
Reviewed by Ulas D. Bayraktar, MD on Apr 9, 2026
