Uptake of Novel Agents (NAs) As First-Line Treatments for Black and White Patients with Chronic Lymphocytic Leukemia (CLL) in the Veterans Health Administration (VHA): A Retrospective Cohort Study
Authors: Lucero Kana Tai , Obodozie-Ofoegbu Obiageri O. , Nooruddin Zohra , Castillo Alyssa , Moore Amanda M. , Ryan Kellie J. , Jones Xavier , Frei Christopher R. 
Published: November 2021

Abstract
Introduction
Since the introduction of NAs in 2013, the treatment paradigm for CLL has changed significantly with the increased uptake of NAs for first line (1L) and refractory CLL. NA have introduced a personalized approach to CLL treatment that considers patient baseline characteristics, individual risk factors and preferences. 1 Despite improvement in survival outcomes with CLL, Black patients with CLL have demonstrated inferior overall survival as compared to White patients. 2 Studies have shown a difference in disease biology between Black and White patients. 3 Differences in disease biology and access to medical care and treatment have contributed to racial disparities. The purpose of this study was to assess the uptake of NAs in the VHA where access to care is equal for both Black and White patients.
Methods:
A retrospective study was conducted which observed adult patients with an ICD code for CLL managed in the VHA from 2014 to 2017. Electronic and manual data was extracted to review start and stop dates for 1L CLL therapies. Data up to twenty years prior to the CLL treatment initiation date was reviewed to define the baseline variables. Descriptive statistics were used to summarize the data, and chi-square and Student's t-tests were used to compare NA use, baseline characteristics, healthcare resource use, and complications. A two-step nominal logistic regression model was used to determine the effect of race on receipt of NAs. Baseline patient characteristics were compared with bivariable statistical tests and variables with a p-value less than 0.10 were subsequently entered into the multivariable nominal logistic regression model. P-values less than 0.05 were considered statistically significant
Results:
The study included 565 patients; 86% were White and 14% were Black. Black patients were younger than White patients with a median age of age 66 and 69 respectively, p&lt; 0.0001 (Table 1). Overall, Black patients were less likely to receive NAs than White patients (14% vs. 26%, p=0.0165) (Table 1). However this difference narrowed over the study period. (Figure 2) Traditional chemotherapy/chemoimmunotherapy (CT/CIT), was more common in Black patients. White and Black patients experienced similar treatment outcomes and health care utilization (Table 2). When all baseline variables listed in Table 1 were compared for Black and White ptients, the following variables had p-values less than 0.10 and were subsequently entered into a multivariant model: patient age (p&lt;0.0001), male sex (p=0.0901), peptic ulcer disease (p=0.0981), deep vein thrombosis (p=0.0976), intestinal disorders (p=0.0252), priority group 7-8 (p=0.0561), use of antihypertensives (p=0.0302), and fiscal year. In the multivariant model, with NA use as the dependent variable, Black race as the independent variable, and divergent baseline characteristics as the covariates, the only variables that were independently predictive of NA use were Black race (p=0.0243, OR=0.47, 95%CI=0.24-0.94) and fiscal year (p=0.0019).
Conclusions:
In this retrospective cohort study, there was a statistically significant difference in the use of NAs between Black and White patients with CLL in the VHA for the study period. However, when NA use was examined by year, the disparity was largest in the early study years with reduced differences in NA utilization over time. Potential limitations of this study include the smaller number of patients, biologic factors that were not captured, and potential confounding factors such as physician experience with NA use. With the introduction of more NAs, the VHA should pay close attention to ensure all patients receive equal access to new therapies. We hope to implement interventions to ensure that patients of all races have equal access to NAs as soon as they are introduced.
References
1. Burger, J, O'Brien, S. Evolution of CLL treatment - from chemoimmunotherapy to targeted and individualized therapy. Nat Rev Clin Oncol. 2018 Aug;15(8):510-527.
2. Sikander Ailawadhi, Dongyun Yang, Nidhi Jain, Mie Mie Thinn, Wendy Cozen, Asher Chanan-Khan; Ethnic Disparities in Chronic Lymphocytic Leukemia Survival: A SEER Database Review. Blood 2012; 120 (21): 757.
3. Flowers, RC, Po, B. Racial differences in chronic lymphocytic leukemia. Digging Depper. 2013 Oct 15;119(20):3593-5.
Figure 1 Figure 1.

Disclosures
Obodozie-Ofoegbu: University of Texas at Austin: Ended employment in the past 24 months. Nooruddin: AstraZeneca: Research Funding. Ryan: AstraZeneca: Current Employment, Current equity holder in publicly-traded company. Jones: AstraZeneca: Research Funding. Frei: AstraZeneca: Research Funding.