Real-world outcomes associated with chronic lymphocytic leukemia (CLL) therapies for patients treated in the United States Veterans Health Administration System

Chronic lymphocytic leukemia is the most predominant leukemia of all the hematologic malignancies. It disproportionately afflicts older male Caucasians. It is classically considered a manageable but incurable disease. Consequent upon diagnosis, several treatment options are available, and the choice of which to use is determined to a large extent by the clinical, biological, and genetic manifestations of the disease. Up until 2014, gold standard for CLL treatment was chemoimmunotherapy-based. The advent of targeted therapy with agents that function at the gateway of dysregulated enzyme pathways, completely transformed the CLL treatment arena. The last decade has witnessed shifts in paradigm and rapidly changing treatment practices, attendant upon several new drug/treatment approvals. What type of shift in uptake and volume of the various classes of CLL agents has occurred due to these changes in pattern.? Our study set to determine the shift in therapies of nine CLL therapies in the Veterans Health Administration System. It described the pharmacoepidemiology of traditional chemotherapies/chemoimmunotherapies (CT/CIT) and the novel agents, in the VHA CLL is a highly variable disease with important patient contributed factors that can affect outcome. Our study also focused on outcomes associated with these therapies, with a view to determining which are important influencers. This was a retrospective study of adults with CLL in the VHA from 10/01/2013 to 5/31/2018. All were followed for at least 6 months. Data were extracted from the VHA electronic health record. Patients came from all 18 Veterans Integrated Service Networks, spanning all 50 states and US territories. Descriptive statistics were used to summarize the data, and chi and student-t-test to compare drug use, outcomes, and complications. Statistical significance was accepted at P<0.05. Our study showed that a total of 1,456 patients across all lines of therapy received at least one of nine CLL therapies of interest. Patients had a median age of 70 years (76% were 65+ and 24% were <65 years). A median age-adjusted Charlson comorbidity score of 5, and 9% had a history of exposure to Agent Orange. Within the period studied, CT/CIT accounted for about 73% of all treatments, while the novel agents use was 27%. Ibrutinib was predominantly used in first and second lines of therapy. Ibrutinib use across all lines of therapy (LOTs) increased steadily while traditional CT/CIT use declined steadily over the study period. However, the traditional chemoimmunotherapies were predominantly used in patients under 65 years old, while ibrutinib was used more on those older than 74 years. A non-significant but higher incidence of diffuse large B cell lymphoma post-index was higher in patients on CT/CIT than those on ibrutinib. Concomitant use of some medications increased the relative risk of death for both the novel agents and the CT/CITs but was seen more with the latter. In conclusion, novel agents are transforming the CLL treatment landscape, Traditional chemoimmunotherapies are still important in a subset of CLL patients. There has been a major shift in the treatment of CLL, with fast adoption of novel agents in the VHA from 2013 to 2018.