Long‐Term Clinical Outcomes, Adherence, Persistence, and Adverse Event Management in Patients With Chronic Lymphocytic Leukemia Treated With Ibrutinib
Santoleri Fiorenzo, Pennese Elsa, Sanna Alessandro, Pittorru Mario, Tonialini Lorenzo, De Bello Federica, Scortechini Ilaria, Guglielmi Sabrina, Ranucci Elena, Schiattone Luana, Carriero Luigi, Costantini AlbertoABSTRACT
Background
Long‐term treatment with Bruton's tyrosine kinase inhibitors has substantially improved outcomes in chronic lymphocytic leukemia (CLL). However, real‐world evidence simultaneously evaluating clinical outcomes, treatment adherence, persistence, and adverse event management remains limited. This study assessed long‐term treatment dynamics and clinical outcomes in patients with CLL receiving ibrutinib in routine clinical practice.
Methods
We conducted a multicenter, retrospective, observational study involving four Italian centers. Adult patients with CLL treated with ibrutinib between January 2016 and June 2024 were included. Clinical records were linked with hospital pharmacy dispensing registries to evaluate progression‐free survival (PFS), overall survival (OS), time to treatment discontinuation (TTD), adherence, persistence, and adverse event management. Adherence was calculated using dispensing data adjusted according to the prescribed daily dose (PDD). Kaplan–Meier analyses were performed for survival outcomes, while multivariable logistic and Cox regression models were used to identify factors associated with adherence and clinical outcomes.
Results
A total of 276 patients were included (47% first‐line, 36% second‐line, and 17% third‐line or later therapy). Mean age was 70 ± 10 years and 63% were male. Adherence remained consistently high across treatment lines and throughout follow‐up, with mean adherence values generally ranging between 0.75 and 0.90. At 8 years, first‐line patients achieved PFS, OS, and TTD rates of 86.4%, 64.5%, and 61.4%, respectively. Corresponding estimates were 72.7%, 49.5%, and 23.1% in second‐line patients and 95.8%, 49.4%, and 53.5% among patients receiving third‐line or later therapy. Adverse drug reactions occurred in 53% of patients; 74% resolved following clinical management. Higher comorbidity burden (CIRS > 6) was independently associated with optimal adherence (OR 2.12, 95% CI 1.12–4.00; p = 0.016) and lower risk of treatment discontinuation (HR 0.36, 95% CI 0.16–0.80; p = 0.013).
Conclusions
Long‐term treatment with ibrutinib was associated with favorable clinical outcomes, sustained adherence, and prolonged treatment persistence in routine clinical practice. Proactive adverse event management and individualized treatment optimization may contribute substantially to maintaining long‐term treatment exposure and maximizing clinical benefit.