Lessons from CLL17: Continuous vs Fixed-Duration Therapy in 1L CLL

Results from the phase 3 CLL17 trial (NCT04608318) are helping clarify the ongoing debate over continuous vs fixed-duration therapy in frontline chronic lymphocytic leukemia (CLL). In an interview with Targeted Oncology, Nicole Lamanna, MD, professor of Medicine and director of the CLL program at Columbia University Irving Medical Center, explains how these findings are shaping treatment discussions with newly diagnosed patients today.

The CLL17 trial directly compared several modern, chemotherapy-free frontline strategies, randomizing patients to continuous treatment with the Bruton tyrosine kinase (BTK) inhibitor ibrutinib (Imbruvica), an all-oral combination of ibrutinib plus venetoclax (Venclexta), or the fixed-duration regimen of venetoclax plus obinutuzumab (Gazyva).¹ Importantly, the study excluded chemoimmunotherapy arms, reflecting a fully modern treatment landscape for CLL.

At approximately 3 years of follow-up, outcomes across the treatment strategies were similar. According to Lamanna, the study demonstrated no significant differences in progression-free survival (PFS) or overall survival between continuous therapy and time-limited approaches. These results provide reassurance that either strategy can be appropriate for many patients and support a more individualized approach to treatment selection.

Lamanna noted that one key concern for both physicians and patients has been whether choosing a fixed-duration regimen might limit future treatment options. The evolving evidence suggests this is not the case. Patients who begin with time-limited therapy can still transition to continuous therapy later if needed, and those who start with continuous therapy can also move to alternative regimens upon progression.

While the overall data support flexibility, some high-risk patients may benefit from a specific strategy. In individuals with adverse genomic features such as TP53 alterations or 17p deletion, early analyses from CLL17 suggest slightly improved PFS with continuous BTK inhibitor–based therapy compared with time-limited regimens.

As follow-up from CLL17 continues to mature, clinicians will look for potential differences emerging over time or within specific molecular subgroups. For now, Lamanna emphasized that both approaches remain effective options, making shared decision-making and patient preference central to frontline CLL care.

REFERENCE

1. Al-Sawaf O, Stumpf J, Zhang C, et al. Fixed-duration versus continuous treatment for chronic lymphocytic leukemia. N Engl J Med. 2026;394(11):1084-1096. doi:10.1056/NEJMoa2515458