Zanubrutinib Holds a 72% 5-Year PFS in del(17p) Front-Line CLL/SLL

Zanubrutinib, a selective next-gen BTK inhibitor, was given as continuous monotherapy to 111 treatment-naïve CLL/SLL patients with high-risk del(17p) in the non-randomized SEQUOIA arm C (NCT03336333). After a median 65.8 months of follow-up, median PFS and OS remain unreached; 60-month estimates are 72% for PFS and 85% for OS. Investigator-assessed ORR reached 97% (18% CR/CRi). Grade ≥3 safety signals per 100 patient-years included infection 33%, neutropenia 16%, hypertension 8%, bleeding 6%, and atrial fibrillation/flutter 5%; 62% of patients are still on drug. For context, 6-year PFS with acalabrutinib monotherapy in del(17p)/TP53-mutated CLL is 56%, and earlier ibrutinib real-world cohorts show inferior durability in this genotype. Zanubrutinib therefore sets a new bar for long-term disease control in this historically refractory subgroup.