A study compared the mainstay treatment approaches for chronic lymphocytic leukemia (CLL) and found that fixed-duration regimens were non-inferior to continuous treatment, offering similar survival and response outcomes.
Results were presented by Othman Al-Sawaf, MD, PhD, of the University Hospital Cologne in Germany, at the 67th ASH Annual Meeting and Exposition.
“This is the first phase 3 trial comparing the main paradigms of continuous [versus] fixed-duration targeted therapy of CLL,” the authors noted of the study that was designed to test the non-inferiority of these two approaches.
The international, randomized, prospective CLL17 trial included 909 previously untreated patients with CLL who were randomized to receive:
- Continuous ibrutinib monotherapy (n=301) given until intolerance or disease progression
- Fixed-duration venetoclax plus obinutuzumab (VO; n=303) given for six cycles followed by six additional cycles of venetoclax monotherapy
- Fixed-duration venetoclax plus ibrutinib (VI; n=305) given with a three-cycle ibrutinib lead-in followed by 12 cycles of combination therapy
As of data cutoff (April 11, 2025), the median duration of observation was 34.2 months. Median patient age was 66 years, most (67.8%) were male, and a third (33.7%) had a creatinine clearance <70 mL/min. The median cumulative illness rating scale score was three.
Few patients (7.6%) had del(17p) and/or TP53 mutations, 56.5% had unmutated IGHV, 19.2% had a complex karyotype, and 53.8% had high CLL-International Prognostic Index scores.
The three-year progression-free survival (PFS) rate (primary endpoint) was 81.1% with VO and 79.4% with VI compared with 81.0% for continuous ibrutinib therapy, “with the upper limit of each adjusted confidence intervals below the pre-defined non-inferiority margin, providing early evidence of non-inferiority,” the authors noted.
The overall response rate was:
- 2% with VO
- 5% with VI
- 0% with continuous ibrutinib
The three-year overall survival rate was:
- 5% with VO
- 0% with VI
- 7% with continuous ibrutinib
The rate of undetectable measurable residual disease (at <10–4) in the peripheral blood was 73.3% with VO, 47.2% with VI, and 0% with continuous ibrutinib.
For patients with unmutated IGHV, the three-year PFS was 75.8% with VO, 78.9% with VI, and 75.8% with continuous ibrutinib.
The most common adverse events occurring in the VO, VI, and continuous ibrutinib arms were infections and infestations (76.3%, 80.2%, 79.9%, respectively), gastrointestinal disorders (59.7%, 74.3%, 63.4%), and blood and lymphatic system disorders (59.0%, 42.9%, 28.5%). Cardiac disorders occurred in 13.9%, 23.8%, and 34.6%, respectively, and secondary cancers were reported in 11.5%, 11.2%, and 18.5%, respectively.
“Early findings indicate that fixed-duration treatment with VO or VI are non-inferior to continuous treatment with [ibrutinib] and may therefore represent the preferred treatment option for [patients] with previously untreated CLL,” the authors concluded.
Reference
Al-Sawaf O, Stumpf J, Zhang C, et al. Fixed-duration versus continuous targeted treatment for previously untreated chronic lymphocytic leukemia: results from the randomized CLL17 trial. Abstract #1. Presented at the 67th American Society of Hematology Annual Meeting and Exposition; December 6-9, 2025; Orlando, Florida.
