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Abstract Introduction: The impact of cancer care and management beyond treatment is significantly high for cancer patients. Due to the complexities of cancer treatment, patients are heavily reliant upon ancillary support often rendered by friends and family. One significant yet unquantifiable impact of cancer on society is productivity loss of both patients and their caregivers. Non-Hodgkin lymphoma is considered largely incurable with a protracted clinical course punctuated with multiple remission and relapses, warranting repeated treatment and intensive clinical testing, which necessitates significant engagement of patients and caregivers. Many patients are members of the workforce at the age of diagnosis. Both working patients and caregivers need time for medical care, which translates to indirect economic impact due to lost productivity. The objectives of this analysis were to evaluate the productivity loss and indirect costs in patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), or Waldenström macroglobulinemia (WM) and their caregivers. Methods: The MarketScan Commercial and Health and Productivity Management databases were used to identify patients with CLL, MCL, MZL, and WM (using ICD-9/ICD-10 codes) who were continuously enrolled for ≥6 months pre- and ≥1 month post-diagnosis (index date) from 1/1/2010 to 12/31/2019. The final study cohort included patients aged 18-64 who were full-time workers with eligibility of absentee, or short-/long-term disability on index date and for ≥1 month in follow-up. Those who were pregnant during the study period were excluded. Adult, full-time employed caregivers, defined as family members covered under the same health plan as the patient, and continuously enrolled ≥6 months pre- and ≥1 month post-index, were also identified. Among those with eligibility, the percentage with a claim of absentee, short- or long-term disability (patients only), and associated productivity time loss and indirect costs during follow-up were examined. Lost wages were calculated using the US Bureau of Labor Statistics 2019 report. For short- or long-term disabilities, mean daily wages were reduced to 70% of typical wages. Productivity time loss and costs were reported per-patient-per-month (PPPM) for each lymphoma. Results: The final patient cohort included 3,450 CLL, 448 MCL, 1,052 MZL and 394 WM patients; the caregiver cohort included 1,435 CLL, 171 MCL, 437 MZL and 190 WM caregivers. Among eligible patients, there were higher proportions of patients that had absentee claims (CLL, 76%; MCL, 72%; MZL, 72%; WM, 82%), followed by short-term disability (CLL, 16%; MCL, 36%; MZL, 18%; WM, 17%) and long-term disability (CLL, 3%; MCL, 10%; MZL, 3%; WM, 3%) (Figure 1A). The proportions of caregivers with absentee claims (CLL, 78%; MCL, 90%; MZL, 69%; WM, 75%) were also higher than those with short-term disability (CLL, 7%; MCL, 10%; MZL, 4%; WM, 8%) (Figure 1B). For all 4 lymphoma types, average illness-related absentee hours were higher in patients than caregivers (CLL, 9.5 vs 6.9; MCL, 44.5 vs 3.6; MZL, 17.0 vs 5.0; WM, 18.2 vs 8.1). A similar pattern was observed for short-term disability days (CLL, 6.9 vs 4.2; MCL, 10.8 vs 3.4; MZL, 7.0 vs 2.2; WM, 6.7 vs 4.8). Average PPPM indirect costs were higher for patients with long-term disability (CLL, $1,433; MCL, $1,233; MZL, $1,302; WM, $2,056) than with short-term disability (CLL, $1,203; MCL, $1,950; MZL, $1,145; WM. $1,177) or absentee claims (CLL, $365; MCL, $1,606; MZL, $612; WM, $662), except for patients with MCL (Figure 2A). Similar trends were observed among caregivers, though the indirect costs due to absenteeism and short-term disability were higher in patients than caregivers (Figure 2B). Conclusions: This real-world evidence study uncovered patients with CLL, MCL, MZL and WM and their caregivers incur substantial disease burden as shown by their productivity loss and indirect costs. Effective treatments that can offer a cure or better remission rates and shorter duration with less toxicity may not only enhance the patients and caregivers' quality of life but also reduce work loss. The availability of oral, targeted therapies has resulted in higher remission rates, durable responses, manageable toxicities and improved quality of life in trials. Future studies are needed to understand the impact of these oral, targeted therapies on patients' and caregivers' productivity. Figure 1 Figure 1. Disclosures Yang: BeiGene, Ltd.: Current Employment. Liu: BeiGene, Ltd.: Current Employment. Irwin: IBM Watson Health: Current Employment; BeiGene, Ltd.: Consultancy. Packnett: IBM Watson Health: Current Employment; BeiGene, Ltd.: Consultancy. Lew: BeiGene, Ltd.: Consultancy; IBM Watson Health: Current Employment. Noxon: BeiGene, Ltd.: Consultancy; IBM Watson Health: Current Employment. Tang: BeiGene, Ltd.: Current Employment. Chanan-Khan: BieGene, Jansen, Ascentage: Consultancy; BeiGene, Jansen, Ascentage: Honoraria; Alpha2 Pharmaceuticals: Patents & Royalties: Tabi; Cellectar: Current equity holder in publicly-traded company; Ascentage, Starton, Cellectar, NonoDev, Alpha2 Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Alpha2 Pharmaceuticals, NonoDev, Starton: Current holder of stock options in a privately-held company; Ascentage: Research Funding.

Abstract Introduction: Chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) are the most common types of leukemia in adults in the United States. The US veteran population, predominantly older males, are at high risk for CLL/SLL, especially with prior exposure to Agent Orange or other herbicides during military service. With the increasing availability of novel agents and associated improved survival, there is a need to assess the real-world evidence of CLL/SLL burden in US veterans, as well as the clinical and economic outcomes associated with current treatments. The objective of this retrospective cohort study was to examine the clinical burden, costs and healthcare resource utilization of CLL/SLL in veterans. Methods: Adults who were newly diagnosed with CLL/SLL were identified in the Veteran Health Administration dataset from October 2014 to September 2019. Eligible patients were required to have at least 2 visits with CLL/SLL diagnosis, and continuous enrollment of 6 months pre- and 3 months post-index date, defined by the first diagnosis date. The study population was further required to have at least 1 CLL/SLL treatment on or after the index date. Treatment regimens were identified by line of therapy and categorized mutually exclusively as: bendamustine-based (alone or in combination) therapy, other chemotherapies, ibrutinib, rituximab-monotherapy, or other regimen. Descriptive analyses were conducted to examine patient sociodemographic characteristics, comorbidities, concurrent medications, and treatment patterns including the frequency and duration of each treatment regimen. Adherence was measured by discontinuation and switching rates. Discontinuation was defined as no treatment for 90 days from the last day of supply during the study period. To ensure only patients who prematurely discontinued chemotherapy treatment and not those who completed their treatment cycles are captured, premature discontinuation was defined as a treatment duration of <90 days for bendamustine-based and <120 days for rituximab monotherapy. Costs and healthcare resource utilization were examined by first-, second-, and third-line therapy. Healthcare resource utilization examined included hospitalization and length-of-stay (LOS). Total costs were reported for all-cause and CLL/SLL-related, and calculated as the sum of inpatient, outpatient and pharmacy costs per-patient-per-month (PPPM). Multivariable logistic regression was conducted to examine factors associated with costs, frequency and LOS of hospitalizations. Results: Among the 13,664 veteran patients diagnosed with CLL/SLL, 79% were in watch-and-wait and the final study population consisted of 2,861 patients who received at least 1 line of CLL/SLL therapy (mean duration=465 days). Most patients were elderly (median age =70 years), white (83%), and male (98%). Approximately 39% of veterans had concurrent use of proton pump inhibitors at baseline. Average time to treatment initiation from diagnosis to first-line therapy was 315 days. A total of 770 (26.9%) patients further received second-line therapy (mean duration of treatment=318 days) and 199 (7.0%) patients received third-line therapy (mean duration of treatment=229 days). Ibrutinib was the most common treatment regimen across all lines of therapy (first-line: 39%; second-line: 55%; third-line: 43%) with discontinuation rates at 59.6%, 60.1%, and 55.2% in first-, second-, third-line therapy respectively (Figure 1 and 2). The CLL/SLL-related hospitalization rate was 39% with an average LOS of 7 days. Total PPPM all-cause and CLL/SLL-related costs were $26,709 and $17,233, respectively; these costs were increased by line of therapy. Controlling for patient clinical and demographic covariates, treatment discontinuation and treatment switching were statistically significant predictors of higher inpatient admissions, LOS of hospitalizations, and costs. Conclusions: This real-world data demonstrated significant clinical and economic burden associated with CLL/SLL among the US veterans. Furthermore, the suboptimal adherence, as reported by high treatment discontinuation rates and its impact on increasing costs and healthcare resource use, highlights the real-world unmet needs of CLL/SLL management in the veteran population. Future studies are needed to further understand the long-term outcomes of each treatment regimen. Figure 1 Figure 1. Disclosures Yang: BeiGene, Ltd.: Current Employment. Liu: BeiGene, Ltd.: Current Employment. Tang: BeiGene, Ltd.: Current Employment. Chanan-Khan: Ascentage: Research Funding; Alpha2 Pharmaceuticals: Patents & Royalties: Tabi; Ascentage, Starton, Cellectar, NonoDev, Alpha2 Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; BeiGene, Jansen, Ascentage: Honoraria; Cellectar: Current equity holder in publicly-traded company; Alpha2 Pharmaceuticals, NonoDev, Starton: Current holder of stock options in a privately-held company; BieGene, Jansen, Ascentage: Consultancy.

Abstract Introduction: Prognostic testing, including immunoglobulin heavy-chain variable region gene (IgHV) mutation status, cytogenetic abnormalities by fluorescence in situ hybridization (FISH), and immunophenotyping has been recommended in all newly diagnosed patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) prior to treatment initiation, and even in previously treated patients in some settings. Recent data have shown that disease with high-risk genetic features is better managed with novel agents than traditional chemoimmunotherapy. As such, the need for testing has become more relevant for disease management. However, there is limited recent data on real-world patterns of testing for risk factor assessment and in-turn, patterns of evidence-based treatment selection. This study aimed to examine: (1) the frequency and results of testing, (2) timing of testing by line of therapy, and (3) factors associated with the receipt of testing. Methods: De-identified data from the Flatiron Health EHR-derived database was used to identify patients who were ≥18 years old with newly-diagnosed CLL/SLL, who had ≥6-month continuous enrollment, and no prior treatment from January 2014 to May 2021. Testing evaluated included IgHV mutation status, FISH cytogenetic (11q deletion [del(11q)], 13q deletion [del(13q)], 17p deletion [del(17p)], Trisomy 12 [+12]) and other biomarkers (including CD38 and ZAP-70) by immunophenotyping. Descriptive analyses were conducted to examine the frequency and results in the overall population, and compared by patient characteristics and across sociodemographic groups. Multivariable logistic regression was conducted to examine factors associated with the likelihood of receiving testing. Statistical significance was determined as a p-value of <0.05. Results: A total of 3,037 CLL patients were included (median age=73, 62.3% male, 74.6% white). The majority of patients (92%) received treatment in community practices, with 54.1% commercially-insured. We observed over half of CLL patients did not receive risk factor testing (Figure 1): IgHV mutation analyses (76.2%, n=2,315), FISH (61.5%, n=1,868) and immunophenotyping (72.1%, n=2,190). Of those who had testing, the majority (99%) had it done once prior to starting first-line therapy. Significant differences in the receipt of testing were observed between different age, gender, race/ethnicity, and regional subgroups (Table 1). Among patients who received testing, the presence of high-risk biomarkers was as follows: unmutated IgHV (56.1%), del(17p) present (14.4%), del(11q) present (16.9%), and CD38 present (30.8%). Compared to patients <65 years, testing results in elderly patients ≥65 years showed a lower presence of unmutated IgHV (53.8%) and del(11q) (15.7%) while higher del(17p) (14.7%) and +12 (28.1%). No significant disparity was observed in white vs. non-white patients except for a lower incidence of mutated IgHV and del(13q) presence. Compared to tested men, tested women had a lower presence of unmutated IgHV (53.9%), del(11q) (11.4%) and CD38+ (25.8%) while higher del(17p) (18.2%). We then investigated the impact of risk testing on therapy selection, and noted that patients with del(17p) had a higher likelihood than those who tested negative (73.6% vs. 48.4%) of being treated with novel agents (ibrutinib, acalabrutinib, or venetoclax). In contrast, 26.4% of those who tested del(17p) present and 39.8% among those who did not get tested received chemotherapy. Multivariable regression showed that patients who were older (≥65 years), female or those living in the west of U.S. were significantly less likely to receive testing. Conclusions: The NCCN guidelines recommend novel agents for patients with high-risk CLL/SLL. Thus, all patients are advised to complete risk-factor testing for both prognostication and selection of optimal, evidence-based therapy. Our real-world data highlights not only a significant gap in testing, but that this suboptimal testing is more common in vulnerable populations. We observed that despite identification of del(17), a quarter of CLL patients failed to receive novel agents in the frontline setting. Our analysis identified an unmet need for further education and refinement of clinical practice. This is necessary to achieve the best clinical outcome in CLL patients through robust risk-assessment testing and optimal therapeutic triaging. Figure 1 Figure 1. Disclosures Chanan-Khan: BieGene, Jansen, Ascentage: Consultancy; Ascentage, Starton, Cellectar, NonoDev, Alpha2 Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Alpha2 Pharmaceuticals: Patents & Royalties: Tabi; Ascentage: Research Funding; Cellectar: Current equity holder in publicly-traded company; Alpha2 Pharmaceuticals, NonoDev, Starton: Current holder of stock options in a privately-held company; BeiGene, Jansen, Ascentage: Honoraria. Yang: BeiGene, Ltd.: Current Employment. Liu: BeiGene, Ltd.: Current Employment. Zimmerman: BeiGene, Ltd.: Current Employment. Tang: BeiGene, Ltd.: Current Employment. Ailawadhi: Ascentage: Research Funding; Medimmune: Research Funding; Pharmacyclics: Consultancy, Research Funding; GSK: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Genentech: Consultancy; Xencor: Research Funding; BMS: Consultancy, Research Funding; Karyopharm: Consultancy; Cellectar: Research Funding; Sanofi: Consultancy; Janssen: Consultancy, Research Funding; AbbVie: Consultancy; Beigene: Consultancy; Takeda: Consultancy.

Abstract Introduction: Chronic lymphocytic leukemia (CLL) is the most frequently diagnosed hematologic cancer, with many patients diagnosed at a later stage in life and typically with comorbidities that often complicate CLL management. Atrial fibrillation (AF) is the most common arrhythmia in the United States and is associated with high hospitalization and mortality rates. While the relationship between CLL and AF has been reported, there is limited real-world evidence on the clinical and economic impact of AF in CLL patients. The objectives of this study were to examine the impact of AF on cardiovascular (stroke, bleeding events, heart failure) and economic (costs and healthcare resource utilization [HRU]) outcomes among patients with CLL. Methods: This retrospective observational study used the IBM MarketScan Research Databases in Treatment Pathways that includes at least a 10-million sample of the commercial and Medicare supplemental claims database. Patients who were at least 18 years, diagnosed with CLL (identified by ICD-9/ICD-10) and continuously enrolled from January 2009 to July 2020 were included. CLL patients were followed up for one year after their first CLL diagnosis date to examine the incidence of AF. Cardiovascular outcomes were evaluated as the incidence of stroke, bleeding events, and heart failure among the CLL patients with and without AF. Costs and HRU were assessed following up until 1 year after the first date of AF, stroke, bleeding events, and heart failure. HRU was evaluated for outpatient, emergency room (ER), inpatient, and pharmacy visits, and by length of stay (LOS) for hospitalizations. Costs were evaluated in overall population and by HRU type. Statistical differences in clinical outcomes between patients with and without AF were compared using chi-square tests. The Mann Whitney Wilcoxon test was used to compare the medians for the HRU and cost outcomes. The associations between AF and hospitalizations as well as costs were evaluated by multivariable logistic regression and generalized linear model, respectively. Statistical significance was determined at a P-value of less than 0.05. Results: Among the total of 23,756 newly diagnosed CLL patients (median age 68 years, 57.83% male) included in the study, 11% had AF within 1 year of the CLL diagnosis. CLL patients who had AF were significantly older (median age: 67 vs 82 years) and had more male patients (56.9% vs 65.1%) compared to CLL patients without AF. Significantly higher rates of stroke (12.67% vs. 4.97%), bleeding events (17.45% vs. 8.53%), and heart failure (31.14% vs. 4.70%) were observed in CLL patients with AF than those without (Figure 1). Compared to the CLL cohort without AF, adjusted regression analysis indicated that overall, CLL cohort with AF was twice as likely to be hospitalized (odds ratio [OR]=2.03) and incurred 44% higher total costs (cost ratio [CR]=1.44). Further examining the impact of AF-related cardiovascular outcomes, we observed that CLL patients with AF who developed stroke, bleeding events, and heart failure had statistically significant higher HRU (outpatient, ER, inpatient, and pharmacy visits), longer LOS, and costs (total, outpatient, pharmacy) than CLL patients without AF. After adjusting for demographic and clinical confounders, significantly higher hospitalization rates and costs were also reported in the CLL cohort who had AF with further stroke (OR=2.59; CR=1.36), bleeding events (OR=3.27; CR=2.03), and heart failure (OR=5.47; CR=2.07) compared to the CLL cohort without AF. Conclusions: The findings of this real-world study demonstrated significantly higher hospitalizations, cardiovascular events, and economic burden incurred by CLL patients who had AF than those without. The presence of stroke, bleeding events, heart failure among CLL patients with AF further increased the HRU and costs. This study highlighted the importance of better disease management, more intentional monitoring for AF and improved CLL therapeutics with a lower risk of AF or cardiovascular toxicity to prevent or minimize the incidence of AF in CLL patients. Figure 1 Figure 1. Disclosures Mohan: BeiGene, Ltd.: Current Employment. Yang: BeiGene, Ltd.: Current Employment. Liu: BeiGene, Ltd.: Current Employment. Dick: IBM Watson Health: Current Employment. Tang: BeiGene, Ltd.: Current Employment. Chanan-Khan: Ascentage: Research Funding; Alpha2 Pharmaceuticals, NonoDev, Starton: Current holder of stock options in a privately-held company; Cellectar: Current equity holder in publicly-traded company; Alpha2 Pharmaceuticals: Patents & Royalties: Tabi; Ascentage, Starton, Cellectar, NonoDev, Alpha2 Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; BeiGene, Jansen, Ascentage: Honoraria; BieGene, Jansen, Ascentage: Consultancy.