Fixed-Duration vs Continuous Therapy—First-Line Choices in CLL

Segment 06: Fixed-Duration vs Continuous Therapy—First-Line Choices in CLL

Treatment selection between continuous and fixed-duration therapies in frontline chronic lymphocytic leukemia (CLL) requires comprehensive shared decision-making discussions that balance multiple clinical and patient-specific factors. Without definitive head-to-head trials comparing all available options, treatment decisions must incorporate disease characteristics, safety profiles, patient preferences, and logistical considerations. For high-risk patients with TP53 disruption, continuous BTK inhibitor therapy appears to offer efficacy advantages based on cross-trial comparisons. However, fixed-duration regimens remain acceptable options when patients understand the potential for shorter progression-free survival. The absence of evidence suggesting that fixed-duration therapy fundamentally alters disease biology in high-risk patients supports this approach, pending longer follow-up data.

Patient time investment emerges as a crucial framework for treatment discussions, helping patients understand the trade-offs between intensive upfront treatment vs ongoing therapy commitments. Fixed-duration approaches require significant initial time investment with frequent clinic visits, laboratory monitoring, and potential infusion sessions, but offer the possibility of treatment-free intervals. Continuous therapy involves smaller but consistent time commitments every few months with regular monitoring and pill-taking routines. Both approaches involve substantial logistical considerations, including laboratory work, results waiting periods, and clinic scheduling that must be factored into patient lifestyle and preferences.

Indirect comparison analyses are increasingly important given the proliferation of treatment options without corresponding head-to-head trials. Recent matching-adjusted indirect comparison studies, such as those comparing zanubrutinib-venetoclax from SEQUOIA to acalabrutinib-venetoclax from AMPLIFY, provide valuable insights despite inherent limitations. These analyses require careful patient-level data adjustments to create comparable populations between studies and must be interpreted with awareness of their methodological constraints. Although the gold standard remains randomized controlled trials, indirect comparisons offer useful evidence for clinical decision-making when multiple statistical models are employed transparently. Such analyses can help inform the lengthy initial discussions with patients that have become necessary given the expanding treatment landscape and the need to individualize therapy selection.