Patterns of Ibrutinib Use, Discontinuation, and Hospitalization Among Patients with Chronic Lymphocytic Leukemia (CLL) in a US Healthcare Claims Database
Authors: To Tu My , Yeh Wei-Shi , Biondo Juliana , Masaquel Anthony S 
Published: October 2019

Abstract
Introduction :
Current treatment options for CLL or small lymphocytic leukemia (SLL) include novel oral therapies that are taken until disease progression. Ibrutinib is approved in frontline and relapsed/refractory CLL and is the most common oral treatment since Food and Drug Administration approval in 2014. Despite favorable responses with ibrutinib, treatment discontinuation occurs (41-50%) (Mato et al. Haematologica 2018; Sharman et al. Blood 2017) and increases the risk of poor overall survival (Follows GA and UK CLL Forum. Poster Presentation 14th International Conference on Malignant Lymphoma Palazzo dei Congressi, Lugano Switzerland, 2017). Previous studies have reported that in addition to disease progression, intolerance and toxicity were primary reasons for discontinuation. However, hospitalizations have not been explored to date. This study used a large US claims database to evaluate ibrutinib treatment patterns and toxicity-related hospitalizations among patients with CLL.
Methods :
A retrospective analysis of Truven Health MarketScan® Commercial Claims Database was conducted. Patients were included if they initiated ibrutinib treatment (index) between 2/12/2014 and 3/31/2017 and were diagnosed with CLL or CLL along with SLL. Patients were excluded if they had other cancers, did not have at least 180 days of continuous enrollment pre-index (baseline), were treated with ibrutinib within this baseline period, or had less than 180 days of observation after ibrutinib initiation.
Patients were categorized into 1 of 3 treatment cohorts: (1) those who had continuous ibrutinib claims without any gap (Users), (2) those who had a treatment gap, but had at least 1 ibrutinib claim after the gap (Retreated), and (3) those who completely discontinued ibrutinib treatment or switched to another treatment (Discontinued/Switched). A gap in treatment was defined as a period of ≥60 days after the end of treatment exposure (Mato et al. Cancer Biology & Therapy 2018). Patient demographics, time to first treatment discontinuation, and frequency of hospital-related adverse events (AEs) were determined for each cohort. AEs were obtained in the 60 days prior to the last ibrutinib claim (pre-discontinuation) and in the exposure period for the last claim plus 60 days after (post-discontinuation). AEs were assessed for the User cohort based on a proxy derived from a median time from initial treatment to discontinuation in the Retreated and Discontinued groups and using the +/- 60-day time window.
Results :
There were 714 patients included in the analyses. Most patients were male (69%) and the average age at CLL diagnosis was 55.8 years. There were 451 (63%) in the User cohort, 96 (13%) in the Retreated cohort, and 167 (24%) in the Discontinued/Switched cohort.
The median time from ibrutinib initiation to end of study observation was 16.8 (6.0-44.2) months. The median time to ibrutinib discontinuation was 4.9 (1.0-40.4) and 6.0 (1.0-34.1) months for the Retreated and Discontinued/Switched cohorts, respectively. For the Retreated cohort, patients were off ibrutinib treatment for a median of 3.2 (2.0-32.0) months before restarting ibrutinib again. Among the Discontinued/Switched cohort, 61% discontinued ibrutinib treatment without receiving any further treatment and 39% switched to another treatment.
Retreated and Discontinued/Switched cohorts had higher hospitalization rates compared to the User cohort. The 5 most common inpatient diagnoses were pneumonia, pancytopenia/neutropenia, fever, sepsis, and atrial fibrillation across both the Retreated and Discontinued/Switched cohorts (Table 1). Discontinued/Switched cohort were more likely to have any hemorrhage diagnosis for hospitalization (6%).
Conclusion :
Consistent with other studies (median follow-up of 17-20 months) (Mato et al. Haematologica 2018; Sharman et al. Blood 2017), the overall treatment discontinuation with ibrutinib in our study was approximately 37% with a median follow-up of 16.8 months. A limitation is that exact reasons for stopping treatment cannot be ascertained from claims data. However, patients who paused or stopped ibrutinib were more likely to have higher rates of hospital-related AEs than those who continued treatment. As treatment discontinuation is likely to occur during a long treatment exposure, oral agents with a finite duration of treatment and with better tolerability are needed for patients with CLL.

Disclosures
To: Genentech, Inc.: Employment, Other: May own stocks/stock options at Roche. Yeh:Genentech, Inc.: Employment, Other: May own stock/stock options at Roche. Biondo:Roche: Equity Ownership; Genentech, Inc.: Employment, Other: May own stocks/stock options at Roche. Masaquel:Genentech, Inc.: Employment, Other: May own stocks/stock options at Roche.