The Healthcare Resource Utilization, Costs, and Predictors of Progression Among Relapsed and Refractory CLL Patients
Authors: Guerin Annie , Ray Saurabh , Gauthier Genevieve , Hsu Ling-I , Zhdanava Maryia , Wu Eric 
Published: October 2019

Abstract
Background: Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia where the majority of patients (pts) experiences a relapse or becomes refractory after a first-line treatment. This study assesses the economic burden associated with early vs late disease progression among pts with relapsed and refractory (R/R) CLL and identifies factors that are associated with further disease progression.
Method: CLL pts with an indicator of R/R disease were selected from the Truven MarketScan database (>25 million commercially insured lives annually; 2000-2013) based on diagnoses and treatment patterns. Pts were ≥18 years in age, continuously enrolled in their health plan for ≥6 months prior to (baseline period) and ≥1 month after the first indicator of R/R CLL. The index date was defined as the date of the first R/R indicator. As a first step, pts who progressed following the first indicator of R/R CLL were identified and classified into two mutually exclusive cohorts: 1) pts with early progression (<12 months after index date) and 2) pts with late progression (≥12 months after index date). Healthcare resource utilization (HRU) and costs ($2013 US) were measured over the period from index date up to end of continuous healthcare plan enrollment (study period) and were compared between early vs late progression cohorts using multivariate generalized linear regression models. HRU and costs were reported per-pt-per-month (PPPM). As a second step, the full sample of pts with R/R CLL was used to identify factors associated with a risk of early progression using Cox proportional hazard models.
Results: Of the 4,387 R/R CLL pts selected, 2,238 (51%) pts had a progression following the first indicator of R/R CLL. Median time to first progression following the index date was 14.5 months. Among pts who progressed, 69.3% had early progression and 30.7% had late progression. Characteristics of pts with early vs late progression were similar in terms of age, sex ratio, and region of residence. The main differences between cohorts were in terms of baseline comorbidities - a higher proportion of pts in the early progression cohort had hypertension, deficiency anemias, and coagulation deficiency. Quan Charlson Comorbidity Index (CCI) was also higher in the early progression cohort compared to the late progression cohort (2.61 vs 2.48, p<.01). Over the study period, the early progression cohort had higher HRU: 54% more inpatient (IP) admissions, 85% more IP days, 27% more emergency room visits, and 31% more outpatient (OP) visits (all p<.01) compared to the late progression cohort. After adjusting for baseline confounding factors, pts in the early progression cohort also had higher total healthcare costs by $3,008 PPPM (mean costs $8,018 vs. $4,639), mainly driven by higher OP (adjusted difference $1,838) and IP (adjusted difference $848) costs (all p<.01). Among the full sample of R/R CLL pts (4,387 pts), time between CLL diagnosis and the firs indicator of R/R CLL (< 12 months; HR=1.20), and comorbidities, including a higher CCI (CCI≥3; HR=1.19), rheumatoid arthritis (HR=1.49), and substance-related and addictive disorders (HR=1.94) were found to be significantly associated with a higher risk of early progression. Results were generally consistent with a sensitivity analysis, where early vs late progression was defined using a 6-months cut-off.
Conclusions: R/R CLL pts who experienced early progression had more comorbidities and incurred significantly higher healthcare resources and costs than pts with late progression, suggesting that delaying progression in the fast progressing R/R CLL pts can reduce the economic burden. Time from CLL diagnosis to R/R CLL and comorbidities were the main predictors of early progression.

Disclosures
Guerin: Janssen Scientific Affairs, Janssen-Ortho, Inc., Merck & Co., Inc., Merck Frosst Canada, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ogilvy Renault, Ortho-Clinical Diagnostics, Inc., Otsuka America Pharmaceutical, Inc.,:Consultancy; Pfizer Canada, Inc.,RX&D, Sanofi, Savient Pharmaceuticals, Inc., Shire Pharmaceuticals Inc., Sunovion Pharmaceuticals Inc.,Takeda Global Research & Development Center, Inc., Takeda Pharmaceuticals U.S.A., Inc: Consultancy; AbbVie Inc., Alcon Laboratories, Bayer Healthcare Pharmaceuticals, LLC, Celgene Corporation, Cempra Inc., Centocor Ortho Biotech, Cooley LLP, Cyberonics, Inc., DLA Piper, Eli Lilly & Company,Forest Laboratories, Inc., Genentech, Inc., GlaxoSmithKline,: Consultancy, Other: Annie Guerin is an employee of Analysis Group Inc, which has received consultancy fees from AbbVie for this research. Ray:AbbVie Inc.: Employment, Other: Stock Holder . Gauthier:Sunovion Pharmaceuticals Inc.,Takeda Pharmaceuticals U.S.A., Inc.: Consultancy, Other: Genevieve Gauthier is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; AbbVie Inc., Celgene Corporation, Eli Lilly & Company, Genentech, Inc., GlaxoSmithKline, Janssen Scientific Affairs, LLC, Novartis Pharmaceuticals Corporation, Pfizer Canada, Inc., Sanofi, Savient Pharmaceuticals, Inc., Shire Pharmaceuticals Inc.,:Consultancy, Other: Genevieve Gauthier is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations. Hsu:AbbVie Inc: Employment, Other: Stock holder . Zhdanava:AbbVie Inc., Genentech, Inc., Merck Frosst Canada, Novartis Pharmaceuticals Corporation,Shire Pharmaceuticals Inc., Takeda Pharmaceuticals U.S.A., Inc.: Other: Maryia Zhdanava is an employee of Analysis Group Inc, which has received consultancy fees from AbbVie for this research. Wu:Celgene Corporation, Centocor Ortho Biotech, Cephalon, Inc., ConvaTec Inc., Corus Pharma, Inc., Eli Lilly & Company, Eli Lilly & Company, Ethicon, Inc., Forest Laboratories, Inc., Genentech, Inc., GlaxoSmithKline, Janssen Global Services, LLC,: Consultancy; Janssen Pharmaceutica, Inc., Janssen Scientific Affairs, LLC, Lilly Research Laboratories, McNeil Consumer & Specialty Pharmaceuticals, MedImmune, LLC, Melinta Therapeutics, Inc., Millennium Pharmaceuticals, Inc.,: Consultancy; AbbVie Inc., Alcon Laboratory, Astellas Pharma Inc., Astellas Pharma US, Inc., AstraZeneca, Barger & Wolen LLP, Bayer Healthcare Pharmaceuticals, LLC, Biosense Webster, Inc., Blue Cross Blue Shield Association, Boehringer Ingelheim, Bristol-Myers Squibb: Consultancy, Other: Eric Q Wu, is an employee of Analysis Group which has received consultancy fees from AbbVie for this research; Molecular Insight Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Ortho McNeil Pharmaceuticals, Inc., Sanofi, Savient Pharmaceuticals, Inc., Shire Pharmaceuticals Inc.,: Consultancy; Takeda Global Research & Development Center, Inc., Takeda Pharmaceuticals U.S.A., Inc., TAP Pharmaceutical Products, Inc., Vertex Pharmaceuticals Incorporated: Consultancy.