Overall survival, adverse events, and economic burden in patients with chronic lymphocytic leukemia receiving systemic therapy: Real‐world evidence from the medicare population

Abstract

Background Information on overall survival (OS) and adverse events (AEs) in patients with chronic lymphocytic leukemia (CLL) is mostly available from clinical trials. We therefore conducted a population‐based retrospective cohort study to assess OS, incidence of AEs, and economic burden in real‐world practice among Medicare patients treated for CLL. Methods Patients with CLL receiving ≥1 systemic therapy from 2013 to 2015 were selected from the Medicare claims database and followed from the start of first observed systemic therapy (index date) through December 2016 or death. OS for patients receiving each of the most commonly observed treatments was estimated by the Kaplan–Meier method. AEs were assessed among patients receiving these treatments across all observed lines of therapy. All‐cause direct medical costs were assessed from the Medicare system perspective. Results Among 7,965 eligible patients across all observed therapy lines, ibrutinib monotherapy (Ibr; n = 2,708), chlorambucil monotherapy (Clb; n = 1,620), and bendamustine/rituximab (BR; n = 1,485) were the most common treatments. For first observed therapy, 24‐month OS estimates for Ibr, Clb, and BR recipients were 69% (95% CI = 68%–71%), 68% (95% CI = 65%–71%), and 79% (95% CI = 77%–81%) respectively. The most frequently recorded AEs in patients receiving these treatments in any observed line of therapy were neutropenia, hypertension, anemia, and infection. For all patients, the mean monthly all‐cause cost during the follow‐up period was $8,974 (SD = $11,562); cost increased by the number of AEs, from $5,144 (SD = $5,409) among those with 1–2 AEs to $10,077 (SD = $12,542) among those with ≥6 AEs. Conclusion Over two‐thirds of patients survived at least 2 years after starting their first observed therapy for CLL. Our findings highlight considerable susceptibility to AEs and unmet medical need in Medicare patients with CLL treated in routine practice. Medicare incurred substantial economic burden following initiation of systemic therapy, and patients with greater numbers of AEs accounted disproportionately for the high overall cost of CLL management.

Systematic Literature Review of Real-World Effectiveness Results Data for First-Line Ibrutinib in Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

“…The 24-month OS rate among patients in the informCLL registry was 91% [ 27 ]. In another study [ 26 ], the 24-month OS rate was considerably lower at 69%; however, that analysis used Medicare data, and the median age of patients was notably higher than those in the registry analysis (76 years vs 69 years), and the patients had a median Charlson Comorbidity Index of 4, indicating a highly comorbid population. Although there was only one study in which 18-month and 30-month landmark estimates for OS was reported—the analysis of 457 patients from the informCLL registry—OS rates were similarly high at those timepoints, with 91% and 89% of patients estimated to be alive at 18 and 30 months, respectively [ 27 ].…”

“…Overall survival among patients with CLL treated with first-line ibrutinib was reported in one full-text article [ 28 ] and five abstracts [ 24 , 26 , 27 , 32 , 35 ]. Data were from multi-center medical records, Veteran’s Health Administration database, Medicare, SEER, and the informCLL registry.…”

“…Upon full-text review, 264 articles were excluded, mainly because of a lack of outcomes of interest (n = 218) or design of interest (n = 25). A total of 12 publications [23][24][25][26][27][28][29][30][31][32][33][34] (including five full-text articles [28][29][30][31]34], one poster [23], and six abstracts [24,26,27,32,33,35]) met the inclusion criteria of reporting real-world effectiveness data from adults treated with first-line ibrutinib in the USA (Fig. 1).…”

“…The 24-month OS rate among patients in the informCLL registry was 91% [27]. In another study [26], the 24-month OS rate was considerably lower at 69%; however, that analysis used Medicare data, and the median age of patients was notably higher than those in the registry analysis (76 years vs 69 years), and the patients had a median Charlson Comorbidity Index of 4, indicating a highly comorbid population.…”

Real‐world evidence on venetoclax in chronic lymphocytic leukemia: The Italian experience

“…45,46 Real-world studies investigate long-term safety and the impact of adverse events (AEs) on dose reductions and treatment discontinuations, 47 and provide important information on healthcare system costs. 48 Moreover, these studies are used to assess prognostic testing and treatment patterns, 49 and to collect data on specific CLL patient populations. 50 Other important information that can be obtained from RWE studies includes comparing real-world response rates to those described in clinical trials, 51 assessing the effectiveness of treatments in heavily pretreated high-risk patients with CLL, 52 or in different age groups, 53 evaluating the sequencing of targeted therapies in CLL, 54,55 as well as defining the impact of specific AEs.…”