Real‐World Treatment Patterns, Tolerability, and Outcomes Among Patients With CLL/SLL Treated With First‐Line Ibrutinib, Acalabrutinib, or Zanubrutinib in the US Community Oncology Setting: A Retrospective Cohort Study
John M. Burke, Ira Zackon, Yunfei Wang, Kathleen M. Aguilar, John Murphy, Brittani Wayne, Jennifer Prescott, Siyang Leng, Inkyu Kim, Diana Chirovsky, Enrico de NigrisABSTRACT
Background
Covalent Bruton tyrosine kinase inhibitors (cBTKis) are standard first‐line (1L) therapies for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). In clinical trials, second‐generation (2G) cBTKis demonstrated better tolerability than ibrutinib, particularly regarding cardiotoxicity; however, real‐world evidence on their use, discontinuation, and tolerability remains limited. This study examined treatment patterns and outcomes of cBTKis in the US community oncology setting.
Methods
CLL/SLL patients who initiated 1L therapy between November 21, 2019 and July 31, 2023 were identified from electronic health records. Kaplan–Meier methods estimated time to treatment discontinuation (TTD), time to next treatment or death (TTNT‐D), real‐world progression‐free survival (rwPFS), and overall survival (OS). Adverse events (AEs) were reported as proportions and incidence rates. Cox proportional hazards models assessed factors associated with TTD. Correlations between rwPFS and OS were evaluated with Kendall's tau.
Results
Among 584 patients, 384 initiated ibrutinib, 150 acalabrutinib, and 50 zanubrutinib. Median follow‐up durations were 35.6, 42.3, and 16.1 months, respectively. Overall, 51.2% discontinued 1L therapy by 24 months and 65.9% by end of follow‐up, most commonly due to AEs (38.4%). Most patients who discontinued 1L treatment did not advance to 2L (61.8%; n = 238/385). Rates of AEs varied across cBTKis. Higher comorbidity burden, poorer performance status, del(17p), bleeding or infection, and ibrutinib (vs. acalabrutinib) were associated with shorter TTD. At 24 months, rwPFS and OS were 72.8% and 81.9%, respectively; medians were not reached. Older age (≥ 65 years) was associated with shorter TTD, TTNT‐D, rwPFS, and OS. Notable correlations were observed between rwPFS and OS.
Conclusions
In this real‑world study, 1L cBTKi discontinuations occurred more frequently than in clinical trials, primarily driven by AEs. Many patients did not receive subsequent therapy. Tolerability was generally consistent with clinical trials, with variance across cBTKis. These findings highlight the unmet need for more tolerable treatment strategies to improve treatment durability and outcomes in real‐world CLL/SLL populations.
Trial Registration
The authors have confirmed clinical trial registration is not needed for this submission.