CLL17 interim analysis: Fixed-duration vs continuous treatment for CLL

Results from the investigator-initiated, phase III, randomized CLL17 trial (NCT04608318), comparing treatment approaches in 909 patients with previously untreated chronic lymphocytic leukemia (CLL), were recently published in The New England Journal of Medicine by Al-Sawaf et al. Patients were randomly assigned to receive continuous ibrutinib (n = 301), or fixed-duration venetoclax + obinutuzumab (n = 303) or venetoclax + ibrutinib (n = 305). The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included measurable residual disease (MRD), overall survival (OS), and safety. 

Key data: At 34.2 months’ median follow-up, the 3-year PFS rates were 81.1% with venetoclax + obinutuzumab, 79.4% with venetoclax + ibrutinib, and 81.0% with ibrutinib. The hazard ratio (HR) for venetoclax + obinutuzumab vs ibrutinib was 0.87 (98.3% confidence interval [CI], 0.54–1.41), and the HR for venetoclax + ibrutinib vs ibrutinib was 0.84 (98.0% CI, 0.53–1.32); the results for each comparison met the criterion for noninferiority. The rates of undetectable MRD in the peripheral blood after the end of treatment were 73.3%, 47.2%, and 0% in patients in the venetoclax + obinutuzumab, venetoclax + ibrutinib, and ibrutinib groups, respectively, while the 3-year OS rates were 91.5%, 96.0%, and 95.7%, respectively. The most common adverse events (AEs) were infections, gastrointestinal disorders, and cytopenias. 

Key learning: Fixed-duration venetoclax + obinutuzumab or venetoclax + ibrutinib demonstrated comparable efficacy with continuous ibrutinib treatment in patients with previously untreated CLL, suggesting that fixed-duration treatment may be considered in this patient population.