Dr Tedeschi on Zanubrutinib in Older Patients With Treatment-Naive CLL/SLL

“All these [data] taken together show that zanubrutinib is feasible, and its toxicity is very manageable in this difficult-to-treat population.”

Alessandra Tedeschi, MD, of ASST Grande Ospedale Metropolitano Niguarda, discussed findings from a subgroup analysis from the phase 3 SEQUOIA trial (NCT03336333) of zanubrutinib (Brukinsa) in patients with treatment-naive chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who were at least 80 years of age, including those with high-risk genomic features.

Subgroup analyses focused on older adults are essential for understanding the efficacy and tolerability of cancer therapies in populations that are often underrepresented in clinical trials, Tedeschi began. A recent analysis of SEQUOIA presented during the 2026 EHA Congress examined outcomes with zanubrutinib monotherapy in patients aged 80 years and older with CLL/SLL, she added. The parent study compared zanubrutinib with immunochemotherapy in patients without 17p deletion and included a separate cohort of patients with 17p-deleted disease, she noted. This subgroup analysis specifically evaluated the oldest patients enrolled in the trial to determine whether advanced age affected treatment outcomes, she underscored.

At a median follow-up of 78.75 months, findings showed that among the subgroup of patients at least 80 years of age treated with zanubrutinib (n = 38), the investigator-assessed progression-free survival estimate was 89.3% (95% CI, 74.0%-95.9%) at 36 months and 63.8% (95% CI, 44.6%-77.8%) at 72 months. The overall response rate reached 100% for this subgroup of patients, including a complete response rate of 18.4%. These long-term data suggest that durable disease control can be achieved even in very elderly patients, Tedeschi said.

Equally important were the safety findings, Tedeschi noted. Treatment discontinuations due to adverse effects (AEs) were infrequent during the first 3 years of therapy, highlighting the feasibility of prolonged treatment, she said. When adjusted for time on therapy, rates of AEs were low and comparable to those seen in age-matched populations from the broader trial, she added.

Collectively, these results support the use of zanubrutinib in patients aged 80 years and older and demonstrate that the agent is both effective and manageable in this difficult-to-treat population, Tedeschi said. The analysis reinforces the importance of evaluating therapies in elderly patients and suggests that advanced age alone should not preclude the use of targeted treatment approaches in CLL, she concluded.