The objective of this post–hoc subgroup analysis of the phase 3 SEQUOIA study was to assess the efficacy and safety of zanubrutinib in patients aged ≥80 years with treatment–naïve chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), including patients with del(17p).
SEQUOIA was a phase 3 study that enrolled treatment–naïve patients with CLL/SLL who were considered unsuitable for fludarabine, cyclophosphamide, and rituximab. Unsuitability was defined as age ≥65 years and/or a Cumulative Illness Rating Scale score >6, creatinine clearance <70 mL/min, and/or a recent history of serious or multiple infections. In Cohort 1/1a, patients without del(17p) were randomized 1:1 to receive continuous zanubrutinib (Arm A) or six cycles of bendamustine plus rituximab (Arm B). Cohort 2 (Arm C) included patients with del(17p), all of whom received continuous zanubrutinib. This post–hoc subgroup analysis included patients aged ≥80 years from both cohorts who received zanubrutinib. Endpoints assessed included overall response rate, complete response rate, progression–free survival, overall survival, and treatment–emergent adverse events.
Among 38 patients aged ≥80 years treated with zanubrutinib, the median age was 81 years (range, 80–87), and 60.5% were male. Del(17p) and/or TP53 mutations were present in 36.8% of patients. Complex karyotype was detected in 16.7% of evaluable patients. Mutated and unmutated IGHV were reported in 36.8% and 57.9% of patients, respectively. Median follow–up was 78.8 months as of October 31, 2025.
The overall response rate in patients aged ≥80 years treated with zanubrutinib was 100.0%, with a complete response rate of 18.4%. The estimated investigator–assessed progression–free survival rate at 72 months was 63.8% (95% CI, 44.6%-77.8%), and the estimated overall survival rate at 72 months was 75.8% (95% CI, 58.6%-86.6%).
Grade ≥3 treatment–emergent adverse events (TEAE) occurred in 78.9% of patients. TEAEs of interest (any grade/grade ≥3) included atrial fibrillation/flutter (15.8%/0%), major hemorrhage (21.1%/13.2%), hypertension (28.9%/18.4%) and infections (76.3%/36.8%). TEAEs led to treatment discontinuation or death in 39.5% and 13.2% of patients, respectively. Infection was the only TEAE leading to death in >1 patient (two cases; pneumonia and meningitis cryptococcal). At data cutoff, 36.8% of patients remained on zanubrutinib.
