Real World Treatment Patterns, Adverse Events and Healthcare Resource Utilization and Costs Among Chronic Lymphocytic Leukemia (CLL) Patients in the United States
Authors: Kabadi Shaum , Le Lisa , Dacosta Byfield Stacey , Olufade Temitope O 
Published: October 2019

Abstract
Background: CLL is one of the most common types of leukemia among adults. Treatment options for CLL have expanded in recent years, but few studies provide contemporary real-world data on treatment patterns, treatment-related adverse events (AEs) and the economic burden associated with these agents. This study aimed to evaluate treatment-related AEs and the healthcare resource utilization (HCRU) and cost associated with the current treatment for chronic lymphocytic leukemia (CLL).
Methods: This retrospective study used medical and pharmacy claims from the Optum Research Database, a large national US database, to identify adults (≥ 18 years old) commercially insured and Medicare Advantage (MA) enrollees. The study included patients with CLL (≥ 2 medical claims at least 7 days apart between July 1, 2012, through May 30, 2017), at least 1 claim for systemic CLL-directed therapy and continuous enrollment for 12 months prior to (baseline period) and ≥ 1 month after the first observed CLL-directed therapy (index date). Patients with systemic CLL-directed therapy during the baseline period or undergoing stem cell transplantation during the entire study period were excluded from analysis. Up to 3 line of therapy (LOT) periods were captured based on timing and receipt of systemic CLL-directed therapy. Cohorts based on the most common regimens received, regardless of LOT sequence, were created. Potential treatment-related AEs (prevalent and incident conditions) during regimen cohorts were identified by ICD-9 and ICD-10 diagnosis codes in position 1 or 2 on claims. All-cause and AE-related healthcare resource utilization and costs (per patient per month (PPPM)) were examined. All analyses were descriptive.
Results: A total of 3292 patients with CLL met all study criteria; 65% were MA enrollees and 35% were commercially insured. Mean age (standard deviation, [SD]) was 71 years (SD 11) with a baseline Charlson comorbidity index score of 3.5 (SD 1.9). During the study period, 31% of patients had ≥ 2 LOTs and 10% had ≥ 3 LOTs. The most common regimens (excluding rituximab maintenance therapy) observed by LOT were; bendamustine + rituximab (23%) during LOT1, ibrutinib (22%) during LOT2 and ibrutinib (17%) during LOT3. Among the study patients, 4,509 LOT periods (LOT1-LOT3) were observed. Of these periods, 3177 accounted for the 5 most common treatment regimens observed: rituximab (excluding maintenance therapy) (30%); bendamustine + rituximab (28%); ibrutinib (20%); obinutuzumab ± chlorambucil (14%); and cyclophosphamide + fludarabine + rituximab (8%). The most common AEs associated with these treatment regimens are reported in the Table.
Conclusions: The most common regimen during LOT1 was bendamustine + rituximab, and was ibrutinib during LOT2 and LOT3.This study provides evidence that occurrence of AEs among patients with CLL receiving systemic anti-cancer therapy in the real-world setting is substantial and associated with significant health care cost. The economic burden associated with increased AEs underscores the need for treatments with fewer AEs.
Figure. Figure.

Disclosures
Kabadi: AstraZeneca: Employment. Le:Optum: Employment; Optum/United Health Group: Equity Ownership. Dacosta Byfield:Optum/United Health Group: Equity Ownership; Optum: Employment. Olufade:AstraZeneca: Employment; AstraZeneca: Equity Ownership.