Background: CLL represents the most common type of leukemia among adults in the US, but current data on the treatment patterns of patients in clinical practice is limited. Standard of care frontline therapy consists of various types of targeted therapy or chemoimmunotherapy (CIT), but it is reserved for patients with advanced-stage disease. Aims: This study aims to describe real-world treatment patterns among patients diagnosed with CLL in the US, with a focus on ibrutinib therapy. Methods: A retrospective database analysis was conducted using the Optum Clinformatics DataMartTM database (01/2007–07/2020). Patients with ≥2 medical encounters with a diagnosis code for CLL or small lymphocytic lymphoma (SLL) on different dates were selected (earliest date was defined as the index date). At least 12 months of continuous enrollment pre-index date (baseline period) and ≥18 years of age as of the index date were required. Patients with a diagnosis for mantle cell lymphoma or with evidence of anticancer therapy (antineoplastic, radiation, or cell therapy) during baseline were excluded. A subset of patients with ≥1 pharmacy claim for ibrutinib was identified. An adapted algorithm developed from previously published studies was used to identify lines of therapy (LOTs). Treatment patterns, including duration of therapy (DOT) and regimens were reported. DOT spanned from LOT initiation up to discontinuation of all agents in the LOT, a switch to another LOT, or the addition of a new agent. Median time to the first line (1L) and from 1L to second line (2L) were evaluated using a Kaplan-Meier analysis (KM) to account for censoring. Results: Among 23,087 patients with CLL, the median age was 74 years and 43% were female. Of these, 1,387 were treated with ibrutinib (median age: 75; female: 38%). Patients had a mean Charlson comorbidity index score of 1.9. Analysis of treatment patterns (Table 1) showed that 7,192 patients (31%) were treated with ≥1 LOT (mean ± standard deviation [SD] DOT of 1L: 1.6 ± 2.0 years), and 10% of patients were treated with ≥2 LOT (mean ± SD DOT of 2L: 1.2 ± 1.7 years). Ibrutinib was used by 907 patients in 1L (DOT in 1L: 1.0 ± 1.1 years) and 617 in subsequent LOTs (DOT in 2L+: 0.9 ± 1.1 years). Median time from index date to 1L initiation was 8.1 years. Of the patients who used antineoplastics therapies in 1L, a majority used CLL-related ones (79%). Most treated patients received targeted therapy (37%; rituximab: 19% and ibrutinib: 12%) and CIT (32%; bendamustine + rituximab: 13% and cyclophosphamide + fludarabine + rituximab: 5%). In 2L, 16% of patients used ibrutinib, 12% a bendamustine + rituximab regimen, and 4% chlorambucil. Median time from 1L initiation to 2L initiation was 4.4 years. Proportion of patients treated with CIT tended to diminish with subsequent LOT, whereas the proportion treated with ibrutinib tended to increase. Image:Summary/Conclusion: This real-world long-term data shows that patients receive their 1L many years after a first CLL diagnosis, with a median time to treatment of ~8 years. Among US patients with CLL, rituximab, bendamustine + rituximab, and ibrutinib were identified as the most used 1L regimens, and the latter two as the most used 2L regimens. As novel therapies are increasingly used, and genetic testing becomes more available, further research will be needed to evaluate the changes in the way CLL is treated and its effects on clinical outcomes.