SEQUOIA: Zanubrutinib Holds Up in CLL’s Toughest Age Group

In an interview with Targeted Oncology at the 2026 European Hematology Association (EHA) Congress, Alessandra Tedeschi, MD, of ASST Grande Ospedale Metropolitano Niguarda, discusses a subgroup analysis of elderly patients enrolled in the phase 3 SEQUOIA trial (NCT03336333), which compared zanubrutinib (Brukinsa) monotherapy with immunochemotherapy in treatment-naive chronic lymphocytic leukemia (CLL).

In this elderly cohort of patients aged 80 years and older, outcomes with zanubrutinib monotherapy were not inferior to the overall study population, with all patients achieving a response. Despite a substantial proportion of high-risk disease, including 17p deletion, efficacy remained consistent. At 72 months of follow-up, progression-free survival reached 64%, highlighting durable disease control in a very advanced-age population.

Importantly, treatment discontinuations due to adverse events were very low during the first 3 years, and time-adjusted adverse event rates were comparable to age-matched populations, supporting a favorable tolerability profile. Overall, these findings underscore the feasibility of continuous Bruton tyrosine kinase (BTK) inhibitor therapy in very elderly patients.

Tedeschi also discusses how these data inform real-world treatment selection. Zanubrutinib, a covalent BTK inhibitor, remains highly effective and generally well tolerated, but patient comorbidities—particularly cardiovascular disease—must be carefully considered before initiation. In patients where BTK inhibitors are not appropriate, anti-BCL2–based regimens may be preferred. However, she notes that the majority of patients may still be candidates for covalent BTK inhibition. Zanubrutinib is favored for its oral administration, avoidance of treatment ramp-up, and manageable safety profile, making it a practical option in routine community practice.