Frontline orelabrutinib monotherapy in chronic lymphocytic leukemia/small lymphocytic lymphoma: a real-world retrospective study

With the advancement of targeted therapy, Bruton’s tyrosine kinase (BTK) inhibitor-based regimens have become the standard treatment for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Orelabrutinib is a novel, potent BTK inhibitor with high selectivity. However, real-world evidence of orelabrutinib in treatment-naive patients with CLL/SLL remains scarce. This study aimed to evaluate the real-world outcomes and safety of orelabrutinib monotherapy in the first-line treatment of CLL/SLL. This single-center retrospective study included 75 patients with CLL/SLL who received orelabrutinib monotherapy as first-line treatment between November 27, 2021, and November 20, 2024. The primary outcome was objective response rate (ORR). Other outcomes included duration of treatment (DOT), progression-free survival (PFS), overall survival (OS), and safety. Among 75 patients, the ORR and disease control rate were both 86.7% (95% confidence interval [CI], 76.8–93.4). With a median follow-up of 30.8 months (range, 2.1–48.1), the median PFS was not reached; the 12- and 24-month PFS rates were 85.1% (95% CI, 77.4–93.6) and 78.0% (95% CI, 69.0-88.2), respectively. The median OS was not reached, with both 12- and 24-month OS rates of 93.3% (95% CI, 87.9–99.2). Treatment-related adverse events (TRAEs) were reported in 68.0% of patients. Grade ≥ 3 TRAEs occurred in 3 (4.0%) patients, including anemia (1/75, 1.3%), neutrophil count decreased (1/75, 1.3%), and lung infection (1/75, 1.3%). No treatment-related deaths were reported. Orelabrutinib demonstrated promising clinical outcomes and an acceptable safety profile in treatment-naïve patients with CLL/SLL in routine clinical practice, providing supportive real-world evidence that warrants confirmation in larger multicenter cohorts.