Healthcare Resource Utilization and Costs of Patients with Relapsed/Refractory Follicular Lymphoma Receiving 3 or More Lines of Therapy

Abstract Background: Follicular lymphoma (FL) is indolent and typically incurable, and patients (pts) often receive multiple lines of therapy (LOTs) throughout their lifetime (Batlevi et al. Blood Cancer J 2020). Options at relapse following first- or second-line anti-CD20 monoclonal antibody (MoAb)-containing regimens remain limited, although approved third- and later-line therapies (3L+) have become available. Few studies have estimated the real-world economic burden of pts with relapsed/refractory (R/R) FL requiring 3L+ treatment. The aim of this study was to examine real-world healthcare resource utilization (HRU) and costs among pts receiving FL therapies in the 3L+ setting. Methods: This retrospective cohort study used administrative claims data from the IQVIA PharMetrics ® Plus, a US commercial claims database. Adult pts who had ≥1 inpatient claim or ≥2 outpatient claims with an FL diagnosis from January 1, 2011 to September 30, 2020 were included. The final 3L+ population was identified by combining two groups: (1) pts newly initiating FL treatment (defined as systemic anti-cancer therapies listed in the National Comprehensive Cancer Network [NCCN] guidelines) between January 1, 2012 and September 30, 2017 and receiving any subsequent 3L FL treatment during the study period; and (2) pts who received a NCCN-recommended 3L+ FL phosphatidylinositol-3-kinase inhibitor (PI3Ki) between January 1, 2012 and March 30, 2020. Group 1 captured pts who received 3L FL therapies by a proxy algorithm for LOT (Optum 2018) based on NCCN guideline-listed therapies, and group 2 captured pts who received newer available PI3Kis, which are only approved in pts who have received ≥2 previous systemic FL therapies. The index date was the 3L treatment initiation date or the initial PI3Ki claim date. All pts had ≥12 months of pre- and ≥6 months of post-index continuous enrollment in medical and pharmacy benefits. Pts with other primary cancers or evidence of histological transformation during the pre-index period, or clinical trial participation during the study period were excluded. All-cause HRU and all-cause and FL-related (i.e. claim with a FL diagnosis in any position) costs (2020 USD) were annualized during the 3L+ treatment period (defined as the period from index 3L+ treatment until the end of the LOT) to mitigate the effects of different follow-up times. Results: Overall, 100 pts who initiated 3L+ FL treatment were included. Of these, 51% of pts were male, and the mean (standard deviation [SD]) age at index and Charlson Comorbidity Index (non-cancer) at baseline were 62 (10.1) years and 0.9 (1.5), respectively. Mean follow-up time was ~2.3 years, and the mean duration of index 3L+ FL treatment was 273 days. Overall, 44 pts (44%) received subsequent treatment. The most common therapy classes received for index 3L+ FL treatment were oral PI3Kis (n=45, 45%), anti-CD20 MoAb monotherapy (n=19, 19%), and chemoimmunotherapy (CIT; n=18, 18%). A summary of all-cause annualized HRU in pts receiving index 3L+ FL treatment is provided by visit type (Table). For all 3L+-treated pts, mean (SD) all-cause annualized total healthcare costs in the 3L+ treatment period were $193,207 ($148,702), and 83% of total healthcare costs were FL-related costs ($159,815 [$138,477]; Figure). Of the most common 3L+ FL therapy classes, CIT had the highest FL-related mean annualized costs ($214,631 [$120,799]), followed by oral PI3Kis ($131,208 [$86,712]), and anti-CD20 MoAb monotherapy ($105,061 [$73,445]). Conclusions: The economic burden of pts with R/R FL requiring 3L+ FL treatment is substantial, with FL-related costs comprising the majority of total healthcare costs. More than 40% of the pts in this analysis needed subsequent treatment, further compounding the challenges faced by this high-risk population. This analysis provides an initial benchmark for ongoing and future evaluations of the economic value of currently available and emerging therapies for multiple relapsed FL, though future studies with larger sample sizes and longer follow-up are warranted. Figure 1 Figure 1. Disclosures Matasar: Pharmacyclics: Honoraria, Research Funding; Memorial Sloan Kettering Cancer Center: Current Employment; Merck Sharp & Dohme: Current holder of individual stocks in a privately-held company; Genentech, Inc.: Consultancy, Honoraria, Research Funding; Merck: Consultancy; GlaxoSmithKline: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; Juno Therapeutics: Consultancy; Janssen: Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Teva: Consultancy; Takeda: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria, Research Funding; IGM Biosciences: Research Funding; Daiichi Sankyo: Consultancy; Rocket Medical: Consultancy, Research Funding; ImmunoVaccine Technologies: Consultancy, Honoraria, Research Funding; TG Therapeutics: Consultancy, Honoraria. Shapouri: F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Ta: Genentech, Inc.: Current Employment. To: F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months; Genentech, Inc.: Current Employment. Wu: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Wang: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Aurinia Pharmaceuticals Inc.: Current equity holder in publicly-traded company; Novavax, Inc.: Current equity holder in publicly-traded company; Oragenics, Inc.: Current equity holder in publicly-traded company; The SPHERE Institute: Ended employment in the past 24 months; TG Therapeutics, Inc.: Current equity holder in publicly-traded company.

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Healthcare Resource Utilization and Sickness Absence in Newly Diagnosed Multiple Myeloma Patients in Sweden: Trends in a Changing Treatment Landscape

Blood ◽

10.1182/blood-2020-137498 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 17-18

Author(s):

Fredrik Borgsten ◽

Xenia Gatopoulou ◽

Marta Pisini ◽

Magnus Tambour ◽

Frida Schain ◽

...

Keyword(s):

Multiple Myeloma ◽

Sickness Absence ◽

Healthcare Resource ◽

Productivity Loss ◽

Healthcare Resource Utilization ◽

Publicly Traded ◽

The Third ◽

The Past ◽

Over Time

Background In the last decades the introduction of novel drugs has greatly improved the prognosis of multiple myeloma (MM) patients. We have investigated healthcare resource utilization and sickness absence-associated productivity loss over time in a population-wide, retrospective registry study in Sweden. Methods 8,693 patients were identified in the National Cancer Register with a MM diagnosis from July 2001 to December 2015 and followed until 2016. Specialized healthcare usage (inpatient admissions and outpatient visits) were obtained from the Patient Register and costs were estimated by weighted DRG codes. For patients under 66 years of age, sickness absence and salary information were obtained by linkage to the LISA Register. Analyses were performed separately on patients who underwent autologous stem cell transplantation (ASCT) (n=1,425) and on non-transplanted patients (n=7,012) and stratified by diagnosis periods 2001-2005, 2006-2010 and 2011-2015 to reflect increased introduction of effective drugs into clinical care. Median age was 60 years in the ASCT group and 75 years in the non-ASCT group. Results The number of MM patients that underwent ASCT increased over time (n= 282 in 2001-2006 to n= 592 in 2011-2015). MM patients diagnosed most recently had improved overall survival (OS), with five-year OS rate increasing from 52% to 58% to 62% for patients diagnosed in 2001-2005, 2006-2010 and 2011-2015, respectively (p<0.0001). Patients diagnosed during 2011-2015 spent on average 20% and 9% less total time in specialized healthcare than patients diagnosed during 2001-2005 and 2006-2010, respectively (adjusting for sex, age at ASCT, weighted comorbidity score at ASCT and per follow-up year and education at ASCT). This decrease was driven by less usage and time in both inpatient and outpatient care. Adjusted sickness absence time decreased by 41% and 38% in the third follow-up year for patients diagnosed during 2011-2015 compared to patients diagnosed during 2001-2005 and 2006-2010, respectively. Productivity loss costs represented about 45% of total costs (healthcare resource costs ~55%) in the first two follow-up years, but decreased over time. The cumulative median per person cost (healthcare- and productivity-related) over the three follow-up years post-diagnosis decreased by 21% in 2011-2015 (€52,273) compared to 2001-2005 (€66,182), despite an 8% increase in three-year OS over the same period. The number of non-ASCT MM patients also increased over time (n=2,053 in 2001-2005 to n= 2,587 in 2011-2015). Median survival increased from 2.5 years to 3.4 years for patients diagnosed during 2001-2005 compared to 2011-2015. Average total time spent in specialized healthcare was reduced by 29% and 12% for patients diagnosed during 2011-2015, compared to patients diagnosed during 2001-2005 and 2006-2010, respectively (adjusting for sex, age at diagnosis, weighted CCS at diagnosis, weighted CCS per follow-up year and education at diagnosis). This was associated with decreased need for inpatient care and a shift towards more outpatient usage. By the third follow-up year, the adjusted sickness absence time in patients diagnosed during 2011-2015 was reduced by 44% and 23% compared to patients diagnosed in 2001-2005 and 2006-2010, respectively. Productivity loss accounted for approximately 15% of total costs (healthcare resource costs ~85%) and was stable over follow-up years. The cumulative median per-person cost (healthcare- and productivity-related) over three follow-up years was similar for patients diagnosed in 2001-2005 (€25,621) and 2011-2015 (€26,592), despite a 12% increase in three-year OS over the same period. Conclusion The availability of new treatment options for MM patients in Sweden over time was associated with less healthcare usage, less time spent in healthcare and lower productivity loss due to sickness absence for both ASCT and non-ASCT-treated patients. These improved clinical and economic outcomes provide policy makers, healthcare providers and physicians with invaluable real-world insights for cost-benefit considerations in the continued development and introduction of effective treatments for MM. Figure 1 Disclosures Borgsten: Janssen: Current Employment. Gatopoulou:Janssen: Current Employment. Pisini:Janssen: Current Employment. Tambour:Janssen: Current Employment, Current equity holder in publicly-traded company. Schain:Schain Research: Current Employment, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months. Jones:Schain Research: Current Employment. Kwok:Schain Research: Other: Internship . Hjortsberg:Janssen: Current Employment.

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Healthcare Resource Utilization and Costs Associated with Venous Thromboembolism Recurrence in Patients with Cancer

Blood ◽

10.1182/blood.v128.22.4734.4734 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4734-4734

Author(s):

Alok A. Khorana ◽

Keith R. McCrae ◽

Dejan Milentijevic ◽

Jonathan Fortier ◽

François Laliberté ◽

...

Keyword(s):

Cancer Patients ◽

Resource Utilization ◽

Healthcare Costs ◽

Research Funding ◽

Healthcare Resource ◽

Healthcare Resource Utilization ◽

Patients With Cancer ◽

Equity Ownership ◽

Recurrent Vte

Abstract Introduction: Patients with cancer are not only at a high risk for developing primary but also recurrent venous thromboembolism (VTE). These events lead to increased burden of cancer management and healthcare costs. It was estimated that all-cause health care costs for cancer patients with VTE were $30,538/patient higher than in those without VTE (Khorana, 2013). To our knowledge, very little information exists on cost of VTE recurrence among cancer patients. The objective of this study was to analyze resource utilization and costs of patients with cancer experiencing a VTE recurrence using a large claims database. Methods: Medical and pharmacy claims from the Humana Database between 1/1/2013 and 05/31/2015 were analyzed. Newly diagnosed cancer patients with a first VTE diagnosis occurring after their first cancer diagnosis and with ≥1 dispensing of an anticoagulant agent within 7 days after their VTE diagnosis, were selected. Baseline characteristics were evaluated during the 6 month period prior to the index VTE. VTE recurrences were defined as hospitalizations with a primary diagnosis of VTE. Patients were classified into two groups: patients who experienced a VTE recurrence and patients who did not. Resource utilization and costs were evaluated for the entire follow up period, starting with the initiation of the anticoagulant therapy until whichever was earlier, end of eligibility or end of data. Healthcare resource utilization evaluated included number of hospitalizations, hospitalization days, emergency room (ER) visits, and outpatient visits. All-cause and VTE-related healthcare resource utilization was evaluated. Comparisons between patients with a VTE recurrence and patients without a VTE recurrence were performed using rate ratios (RR) and statistical differences between groups as well as 95% confidence intervals [95% CI] were calculated using Poisson regression models. All-cause and VTE-related healthcare costs were evaluated in per-patient-per-year (PPPY) and compared using mean cost difference. Results: A total of 2,428 newly diagnosed cancer patients who developed VTE and were treated with anticoagulants were identified. Of these, 413 (17.1%) experienced recurrent VTE during the follow up period. Patients who developed recurrent VTE and those who did not were similar in terms of age, gender, race, and region. No statistically significant differences between groups were observed in Charlson comorbidity index or in selected comorbidities during the 6 month baseline period. However, more patients with recurrent VTE recurrence had their index VTE documented during a hospitalization (61.3% vs. 55.4%, p=0.03). Patients with a VTE recurrence had significantly more ER and outpatient visits at baseline compared to those without recurrence, but no statistically significant difference was observed in baseline total healthcare costs ($29,352 vs. $27,955, p=0.44, respectively). The mean follow-up was similar between groups: 9.6 months for patients experiencing a VTE recurrence and 9.3 months for patients without a VTE recurrence (p=0.4059). Patients with a VTE recurrence had higher all-cause resource utilization rates (RRs; 95% CI) compared to patients without a VTE recurrence (hospitalization [2.37; 2.23 - 2.52], hospitalization days [2.64; 2.57 - 2.72], ER visits [1.62; 1.48 - 1.76], and outpatient visits [1.26; 1.24 - 1.28]). The rates of VTE-related hospitalization and VTE-related hospitalization days were close to $30,000 higher in patients with a VTE recurrence (Figure 1). The all-cause healthcare costs were $84,708 PPPY in patients with a VTE recurrence compared to $44,903 in patients without a VTE recurrence. The difference was mainly explained by lower VTE-related hospitalization costs (Figure 2). Conclusion: This real-world claims analysis showed that cancer patients with recurrent VTE consume significantly more healthcare resources. Total healthcare costs were nearly 2-fold higher in cohort with than in cohort without VTE recurrence. Close to 75% of the total cost difference was associated with VTE recurrence. VTE-related costs were ~4-fold higher in cohort with than in cohort without VTE recurrence. Reducing VTE recurrence in patients with cancer could lead to substantial healthcare cost savings. Figure 1 VTE-Related Healthcare Resource Utilization Figure 1. VTE-Related Healthcare Resource Utilization Figure 2 VTE-Related Healthcare Costs, PPPY Figure 2. VTE-Related Healthcare Costs, PPPY Disclosures Khorana: Pfizer: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Halozyme: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Janssen Scientific Affairs, LLC: Consultancy, Honoraria, Research Funding; Leo: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria. McCrae:Janssen: Membership on an entity's Board of Directors or advisory committees. Milentijevic:Janssen Scientific Affairs: Employment, Equity Ownership. Fortier:Janssen Pharmaceuticals: Research Funding. Laliberté:Janssen Scientific Affairs: Research Funding. Crivera:Janssen Scientific Affairs, LLC, Raritan, New Jersey: Employment, Equity Ownership. Lefebvre:Janssen Scientific Affairs: Research Funding. Schein:Johnson & Johnson: Employment, Equity Ownership, Other: Own in excess of $10,000 of J&J stock.

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Annual Healthcare Resource Utilization and Costs in US Patients Diagnosed with Relapsed Acute Myeloid Leukemia

Blood ◽

10.1182/blood-2020-136762 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 13-14

Author(s):

Ashley Tabah ◽

Russell L. Knoth ◽

David Huggar ◽

Ronda Copher ◽

Zhun Cao ◽

...

Keyword(s):

Outpatient Treatment ◽

Myeloid Leukemia ◽

Research Funding ◽

Index Date ◽

Healthcare Resource ◽

Healthcare Resource Utilization ◽

Hospital Treatment ◽

Median Cost ◽

Publicly Traded

Introduction: Acute myeloid leukemia (AML) is a malignant form of bone marrow cancer commonly diagnosed in older adults. The age-adjusted incidence of AML in the USA is 4.3 per 100,000, with a median age of 68 years at diagnosis. Once diagnosed, treatment options include intensive chemotherapy to induce remission followed by post-remission therapies, including stem cell transplantation, repeated rounds of intensive chemotherapy to achieve durable disease control, or supportive care. Prognosis following relapse is poor with a median survival of 8-10 months. While previous studies have shown that much of this time following relapse is spent in an inpatient or outpatient setting, few studies have looked at the frequency and costs of this healthcare utilization. This study examined annual healthcare resource utilization and associated costs incurred in patients diagnosed with relapsed AML. Methods: A retrospective analysis was conducted in the Premier Healthcare Database, a nationally representative, all-payer hospital administrative database containing more than 1 billion inpatient and hospital-based outpatient encounters. Using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes for AML in relapse, the study identified adult patients during the period from January 1, 2016 to March 31, 2019. The date of the first encounter with a relapse diagnosis served as the index date. Patients were followed from index date to inpatient death, one year post-relapse, or end of study period (September 30, 2019). Unadjusted descriptive analyses were performed to describe patient demographics, hospital characteristics, and comorbid conditions, as well as outcomes of interest, including outpatient treatment days, inpatient and intensive care unit (ICU) admissions, and associated costs. Results: A total of 2,290 patients were identified for inclusion in the study. Mean age was 61.2 years (median 65.0 years) and 46.9% were female. Healthcare coverage was Medicare (51.2%), commercial insurance (29.1%), Medicaid (13.8%), or other (5.9%). Mean Charlson Comorbidity Index was 4.02 (SD 2.66) and common comorbidities were diabetes (31.0%), congestive heart failure (19.5%), and chronic obstructive pulmonary disease (19.0%). Patients' length of follow-up varied: < 90 days (49.4%), ≥ 180 days (32.8%), and ≥ 360 days (16.8%). During the 1-year follow-up period, patients were seen in the outpatient hospital treatment setting for a median of 7.0 (IQR 2-19) days. In addition to outpatient treatment, patients incurred a total of 1,798 inpatient hospitalizations (median 2.0 per patient, IQR 1-3), with a median length of stay (LOS) of 10.0 (IQR 6-19) days. Among hospitalized patients, 554 (30.8%) included an ICU admission with a median LOS of 3.0 (IQR 1-5) days per admission. Median cost per day for outpatient treatment was $1,039 (IQR $487-2,305) and patients incurred a median cost of $6,569 (IQR $1,872-23,542) in this setting. For hospitalizations, median cost of an inpatient stay was $21,592 (IQR $9,852-45,000). Cost of an ICU admission during a hospital stay was $13,348 (IQR $6,115-28,266). Hospital treatment costs incurred by this cohort of patients in the year following relapse totaled $169 million, of which 82% ($139 million) was attributable to the inpatient setting. Conclusions: After a relapse of AML, patients are commonly admitted to the hospital, oftentimes to the ICU, and incur substantial costs associated with treatment. These results suggest that cost savings could be realized with therapies that would forestall relapse and improve survival in patients with AML. Disclosures Tabah: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Knoth:Bristol Myers Squibb: Current Employment. Huggar:FibroGen: Current equity holder in publicly-traded company; Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company; Karyopharm Therapeutics: Current equity holder in publicly-traded company. Copher:Bristol Myers Squibb: Current Employment. Cao:Bristol Myers Squibb: Research Funding; Precision Xtract: Current Employment. Lipkin:Premier Inc.: Current Employment; Bristol Myers Squibb: Other: Premier Inc. received funding from BMS to conduct this research. Leblanc:UpToDate: Patents & Royalties: Royalties; Agios, AbbVie, and Bristol Myers Squibb/Celgene: Speakers Bureau; American Cancer Society, BMS, Duke University, NINR/NIH, Jazz Pharmaceuticals, Seattle Genetics: Research Funding; AbbVie, Agios, Amgen, AstraZeneca, CareVive, BMS/Celgene, Daiichi-Sankyo, Flatiron, Helsinn, Heron, Otsuka, Medtronic, Pfizer, Seattle Genetics, Welvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Research Funding.

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Healthcare Resource Utilization Trends over Time with Continuous Lenalidomide Treatment (Tx) in Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM)

Blood ◽

10.1182/blood.v124.21.1326.1326 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1326-1326

Author(s):

Katja Weisel ◽

Dan T. Vogl ◽

Michel Delforge ◽

Kevin Song ◽

Meletios Dimopoulos ◽

...

Keyword(s):

Multiple Myeloma ◽

Resource Utilization ◽

Research Funding ◽

Healthcare Resource ◽

Healthcare Resource Utilization ◽

Medical Utilization ◽

Fixed Duration ◽

Advisory Committees ◽

Over Time

Abstract Introduction: Multiple myeloma (MM) is an incurable hematologic condition that is associated with high Tx costs. Resource consumption is driven by hospitalization and medical utilization, which is highest during periods of uncontrolled disease, such as after diagnosis and during relapses (De Portu 2013). In the pivotal phase 3 FIRST trial, continuous Tx with lenalidomide plus low-dose dexamethasone (Rd) was compared with fixed-duration Rd (Rd18) or fixed-duration combination Tx with melphalan, prednisone, and thalidomide (MPT), each for 18 months (mos), in NDMM pts who were ineligible for stem cell transplantation. Continuous Rd extended progression-free survival (PFS) and overall survival (interim analysis) vs. MPT. However, it is still unclear whether extending Tx duration with Rd adversely affects healthcare resource utilization. This analysis quantifies the rates of hospitalizations and medical utilization with continuous Rd over time based on data collected in the FIRST trial. Methods: The FIRST trial (N = 1,623) was a pivotal multinational, randomized, open-label study with a median follow up of 37 mos. Non-protocol-driven resource-use data was collected until subjects discontinued study Tx. To assess whether continuous Rd increases healthcare resource utilization over time, the rates of resource utilization for subjects treated with continuous Rd (N = 535) were plotted for up to 48 mos. In addition, hospitalization and medical utilization rates during the Tx period (18 mos) were estimated and compared between the 2 fixed-duration Tx arms. Results: Resource utilization amongst pts treated with continuous Rd declined over time (Figure). The annualized hospitalization rate in the first 3 mos was 3.2 times higher than the average rate for the remaining 45 mos of follow-up (2.02 vs. 0.62), and 4.2 times higher for medical utilization (5.66 vs. 1.34). After 4 years (yrs) of continuous Rd Tx, hospitalization and medical utilization rates were estimated to be 83% and 84% lower than those observed in the first 3 mos of Tx, reflecting the long-term disease control observed with continuous Rd in the FIRST trial. The highest hospitalization rates were associated with infections (0.20 per patient year), cardiovascular disorders (0.06), and respiratory and thoracic disorders (0.05). The mean (standard deviation) length of stay per admission was 14.08 (21.19) days. The highest medical utilization rates were associated with blood transfusions (0.76 interventions per patient year), general imaging procedures (0.21), respiratory and thoracic imaging procedures (0.20), and therapeutic interventions (0.09).The hospitalization rates for the fixed dose Tx arms were 0.91 (Rd18) and 0.79 (MPT) per patient year of follow-up during the Tx period of 18 mos, resulting in a rate ratio (RR) of 1.15 (1.01–1.30). The equivalent rates for medical utilization were 3.00 (Rd18) and 2.86 (MPT) medical interventions per patient year (RR = 1.05 [0.98–1.12]). Conclusions: The rates of resource utilization among pts treated with continuous Rd dropped substantially after the first 3 mos of Tx, and then gradually declined as Tx duration increased. The findings suggest that continuous Tx with Rd does not further increase resource utilization in hospitalizations and medical utilization compared to fixed-duration Tx. A comparison between the 2 fixed arms showed a 15% increase in hospitalization with Rd18 vs. MPT, and no differences in medical utilization between the 2 arms. A limitation of this analysis is that the resources were collected only while pts were receiving their respective Txs. Future analysis should include all costs generated by healthcare resources throughout pts Tx, including Tx-free intervals, and the costs associated with relapses. Figure 1: Hospitalization and medical utilization rates per patient year for patients treated with continuous Rd Figure 1:. Hospitalization and medical utilization rates per patient year for patients treated with continuous Rd Disclosures Weisel: BMS: Consultancy; Onyx: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene Corporation: Consultancy, Honoraria; Noxxon: Consultancy. Off Label Use: Lenalidomide used in newly diagnosed multiple myeloma patients. Vogl:Amgen: Consultancy; Millennium/Takeda: Research Funding; GSK: Research Funding; Acetylon: Research Funding; Celgene Corporation: Consultancy. Delforge:Janssen: Honoraria; Celgene Corporation: Honoraria. Song:Celgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Dimopoulos:Celgene Corporation: Consultancy, Honoraria. Cavenagh:Celgene Corporation: Honoraria. Hulin:Celgene Corporation: Honoraria. Foá:Celgene Corporation: Consultancy. Oriol:Janssen: Consultancy, Speakers Bureau; Celgene Corporation: Consultancy, Speakers Bureau. Guo:Celgene Corporation: Consultancy. Monzini:Celgene Corporation: Employment, Equity Ownership. Van Oostendorp:Celgene: Employment. Ervin-Haynes:Celgene: Employment. Facon:Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

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Time to Next Treatment, Healthcare Resource Utilization, and Healthcare Costs Among Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Following First-Line Ibrutinib

Blood ◽

10.1182/blood-2021-145117 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4016-4016

Author(s):

Swetha Challagulla ◽

Bruno Emond ◽

Raisa R. Volodarsky ◽

Alex Young ◽

Ameur Manceur ◽

...

Keyword(s):

Healthcare Costs ◽

Healthcare Resource ◽

Healthcare Resource Utilization ◽

Lymphocytic Leukemia ◽

Emergency Room Visits ◽

Small Lymphocytic Lymphoma ◽

Publicly Traded ◽

First Line ◽

Treatment Regimens ◽

Outpatient Visits

Abstract Background: Ibrutinib is an oral once-daily Bruton's tyrosine kinase inhibitor (BTKi) and is the only targeted treatment that has demonstrated significant progression-free survival (PFS) and overall survival (OS) benefit in multiple phase 3 trials for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). With ibrutinib established as a preferred first-line (1L) treatment option, it is important to better understand the treatment sequence after 1L ibrutinib and the characteristics of patients who are treated with a second-line (2L) therapy. Using a real-world US administrative claims database, this study aimed to compare time to next treatment (TTNT), healthcare resource utilization (HRU), and healthcare costs between different 2L treatment regimens (cohorts) used after ibrutinib. Methods: Adults with CLL/SLL treated with 1L ibrutinib were identified in a US claims database (Optum's de-identified Clinformatics ® Data Mart Database; 02/12/2013-03/31/2020). Those receiving a 2L therapy were considered eligible for the study. Retreatment with ibrutinib, in-class switch to another BTKi, or treatment with anti-CD20 immunotherapy-only were not considered eligible 2L treatment options for this evaluation. The most commonly used treatment regimens were categorized into the following clinically-relevant treatment cohorts: 1) chemoimmunotherapy (CIT) or chemotherapy (CT)-only, and 2) venetoclax (VEN)- or idelalisib (IDELA)-based regimens (monotherapy or combination regimens). Comparisons of TTNT, HRU (inpatient admissions, outpatient visits, emergency room visits, other ancillary services), and per patient per month healthcare costs (inpatient admissions, outpatient visits, emergency room visits, other ancillary services, pharmacy) were evaluated based on the sum of the payer and patient paid amount during 2L treatment. Comparisons were adjusted using multivariate regression including confounders observed in the baseline period and during 1L ibrutinib therapy. For costs and HRU, 95% confidence intervals and p-values were obtained from 499 bootstrap resamples. Results: A total of 132 CLL/SLL patients who received ibrutinib as a 1L treatment and had a subsequent eligible 2L therapy were included; mean age was 74 years old, 64% were male. Eligible patients received 2L CIT/CT-only (63/132, 48%), or VEN/IDELA-based regimens (69/132, 52%). TTNT was significantly longer for 2L VEN/IDELA-based regimens than for CIT/CT (hazard ratio at 12 months: 0.37; P=0.0337) (Figure 1). The number of outpatient visits for antineoplastic drug administration was significantly lower for patients receiving 2L VEN/IDELA-based regimens compared to CIT/CT (rate ratio=0.44; P=0.004). Total mean monthly healthcare cost (includes CLL/SLL and non-CLL/SLL-related medical/pharmacy costs) was $1,754 higher, but not significantly different (P=0.593), for patients receiving VEN/IDELA-based regimens compared with CIT/CT (Figure 2). Total mean monthly medical cost (non-pharmacy) was significantly lower ($-5,202; P=0.036) for patients receiving VEN/IDELA-based regimens compared to CIT/CT (Figure 2). Conclusions: This study demonstrates that VEN/IDELA-based regimens may be a more viable treatment option post-1L ibrutinib use for CLL/SLL patients compared to CIT/CT. When compared to 2L CIT/CT, use of VEN/IDELA-based regimens post-1L ibrutinib use was associated with significantly longer TTNT and lower medical costs, signifying reduced disease burden to the patients and lessened burden to the healthcare system. These findings also suggest that treatment convenience associated with 2L oral targeted regimens may play an important role in improving treatment outcomes. These results support the need for evaluating treatment sequencing strategies in the real-world setting to further improve clinical outcomes and reduce the burden of total cost of care for patients with CLL/SLL. Figure 1 Figure 1. Disclosures Challagulla: Pharmacyclics LLC, an AbbVie Company: Current Employment; AbbVie: Current equity holder in publicly-traded company. Emond: Janssen: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy; GlaxoSmithKline: Consultancy. Volodarsky: Pharmacyclics LLC, an AbbVie Company: Current Employment; AbbVie: Current equity holder in publicly-traded company. Young: AbbVie: Current equity holder in publicly-traded company; Pharmacyclics LLC, an AbbVie Company: Current Employment. Manceur: AbbVie: Consultancy; Actelion, part of the Janssen Pharmaceutical Companies of Johnson & Johnson: Consultancy; Bristol-Myers Squibb: Consultancy; Daiichi-Sankyo: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy. Karve: AbbVie: Current Employment, Current equity holder in publicly-traded company.

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Unmet Medical Need Among Elderly Patients with Previously Untreated DLBCL Characterized Using Real-World Data in the United States

Blood ◽

10.1182/blood-2020-136271 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 6-8 ◽

Cited By ~ 1

Author(s):

Ashwini Shewade ◽

Adam J Olszewski ◽

Nelson Pace ◽

Andy Surinach ◽

Gila Sellam ◽

...

Keyword(s):

Elderly Patients ◽

Real World ◽

Research Funding ◽

Publicly Traded ◽

Real World Data ◽

World Data ◽

Reduced Dose ◽

The Past ◽

Medical Need

Introduction: Diffuse large B-cell lymphoma (DLBCL) is a significant source of cancer morbidity and mortality. More than half of all newly diagnosed patients are older than 65 years, among whom the 5-year relative survival rate is 54% (SEER 2020). Prior research has shown that not all elderly patients (≥80 years old) receive R-CHOP or mini-R-CHOP regimens as the first line of therapy (LoT); those who do not may have suboptimal outcomes (Williams, et al. Cancer 2015; Hamlin, et al. Oncologist 2014; Juul, et al. Eur J Cancer 2018). This study leverages two real-world data (RWD) sources, Flatiron Health (FH) electronic health record-derived de-identified database and SEER-Medicare (SEER-M) to characterize elderly patients with DLBCL (including observed treatment patterns), summarize overall survival (OS) outcomes, and identify unmet medical needs in this population. Methods: RWD from FH included patients with a DLBCL diagnosis on or after January 1, 2011, with follow-up until May 31, 2020. The SEER-M database is a linkage of two population-based RWD sources: the SEER Cancer Registry and Medicare claims database. RWD from SEER-M for this study included patients with a DLBCL diagnosis between January 1, 2011 and December 31, 2015, with follow-up until December 31, 2016. All fee-for-service Medicare enrollees in SEER-M had to have complete claims. RWD for basic demographics, treatments and outcomes were analyzed from both datasets; FH's database included data on certain clinical characteristics including granularity for dosing data when available, in comparison to SEER-M. This descriptive analysis included patients who were aged ≥80 years at diagnosis. Among patients in the FH database who received R-CHOP as first LoT and had available dosing data, those who received <80% of standard full doses for cyclophosphamide (750mg/m2) and doxorubicin (50mg/m2) at first administration were classified as "reduced-dose" R-CHOP. OS data were summarized using an unadjusted Kaplan-Meier survival function and 95% confidence intervals (CI). Results: The study included 725 patients from the FH database and 2613 patients from the SEER-M database; patient characteristics and outcomes were generally consistent between the two datasets. In total, 16% and 35% of the elderly patients had no record of systemic treatment in FH and SEER-M respectively (Table). More than half of the treated patients received R-CHOP in the first LoT (63% and 53% in FH and SEER-M, respectively); other patients received attenuated regimens, including rituximab plus bendamustine (R-Benda), rituximab plus cyclophosphamide, vincristine and prednisolone (R-CVP), and rituximab (R) monotherapy. Patients who received R-CHOP in the first LoT had numerically longer median OS (Flatiron: 55.0 months [95% CI: 41.8-NA]; SEER-M: 50.7 months [95% CI: 45.9-62.9]) compared with those who received other regimens (Figure A, B). Untreated patients had a median survival of 3.1 months (95% CI: 2.3-5.2) in the Flatiron dataset and 2.0 months (95% CI: 1.8-2.2) in the SEER-M dataset. Among those who received R-CHOP and with available dosing data, 51% received reduced-dose R-CHOP in the first LoT and OS appeared shorter than for patients who received full-dose R-CHOP (Figure C). Conclusions: Despite differences between the databases, RWD in FH and SEER-M both demonstrate considerable variation in the regimens received by elderly DLBCL patients, with 16-35% receiving no treatment and >50% receiving attenuated regimens including reduced-dose R-CHOP. Patients receiving regimens other than R-CHOP had a numerically lower survival probability compared with the standard of care (SoC) R-CHOP/reduced-dose R-CHOP. These data show a high unmet medical need among elderly patients with DLBCL who may not be able to tolerate immunochemotherapy regimens that have been evaluated in trials for a carefully selected patient population. Further research will aim to assess prognostic factors at the time of treatment initiation, as well as gather information on comorbidities and other factors that may prevent elderly patients from receiving SoC R-CHOP; these patients may be candidates for better-tolerated novel approaches. Disclosures Shewade: Genentech, Inc.: Current Employment. Olszewski:TG Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding; Genentech, Inc.: Research Funding; Spectrum Pharmaceuticals: Research Funding. Pace:Genentech, Inc.: Current Employment; Exponent: Ended employment in the past 24 months; Prior employer was a consulting firm. No expert testimony given. No relevant consulting work done.: Consultancy. Surinach:Seattle Genetics: Research Funding. Sellam:F. Hoffmann-La Roche: Current Employment. Mueller:Genentech, Inc.: Current Employment, Ended employment in the past 24 months; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. O'Hear:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company.

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Greater Red Blood Cell Transfusion Burden Is Associated with More Healthcare Resource Utilization in Patients with Beta-Thalassemia

Blood ◽

10.1182/blood-2019-122747 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5790-5790

Author(s):

Chao-Hsiun Tang ◽

Wesley Furnback ◽

Bruce C.M. Wang ◽

Jackson Tang ◽

Vicky Wei-Hsuen Huang ◽

...

Keyword(s):

Research Funding ◽

Index Date ◽

Hospital Admissions ◽

Healthcare Resource ◽

Healthcare Resource Utilization ◽

Red Blood Cell Transfusion ◽

Beta Thalassemia ◽

Outpatient Visits ◽

Equity Ownership

Introduction: Previous studies have examined the total healthcare resource utilization (HCRU) of patients with beta-thalassemia in relation to the general population. However, limited studies have examined the impact of red blood cell transfusion (RBCT) burden on broad aspects of HCRU beyond transfusion costs among patients with beta-thalassemia. Methods: Patients with beta-thalassemia in Taiwan's National Health Insurance Research Database (NHIRD) in 2016 were identified (International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] of D56.1). The index date was the first medical claim in the database after 2001. Identified patients were followed from the index date until the end of the study period (December 31, 2016). During the follow-up period, RBCT units and HCRU (all-cause and thalassemia-related) were measured. Thalassemia-related HCRU was defined as any HCRU claim accompanied by a thalassemia or beta-thalassemia diagnosis code. To control for the different lengths of follow-up between patients, both RBCT units and HCRU were reported as the average per 12 weeks over the entire follow-up period. Patients were categorized into 4 cohorts based on the average number of RBCT units received per 12 weeks during follow-up: 0 RBCT units; > 0 to < 6 RBCT units; ≥ 6 to < 12 RBCT units; or ≥ 12 RBCT units. HCRU outcomes of interest were hospital admissions, hospitalized days, outpatient visits, and emergency room (ER) visits. Descriptive statistics were computed to describe HCRU observed in each cohort. Results: A total of 2,984 patients with beta-thalassemia were included in the analysis, with a mean follow-up of 6.87 years. Mean age at index was 37.8 (standard deviation 23.7) years, and 1,903 (63.8%) patients were female. A total of 1,616 (54.2%) patients did not receive RBCT units during the follow-up period. Of the remaining 1,368 patients, 1,112 (81.3%) received > 0 to < 6 RBCT units, 112 (8.2%) received ≥ 6 to < 12 RBCT units, and 144 (10.5%) received ≥ 12 RBCT units per 12 weeks during follow-up. Mean all-cause and thalassemia-related HCRU was higher for transfused patients than for non-transfused patients across all HCRU categories. Thalassemia-related hospital admissions, hospitalized days, and outpatient days all increased as the transfusion burden increased. Patients in the cohort with the highest average transfusion burden (≥ 12 RBCT units per 12 weeks) had numerically greater mean thalassemia-related hospital admissions (0.5; standard error [SE] = 0.04), hospitalized days (2.5; SE = 0.21), and outpatient visits (4.9; SE = 0.41) than the other cohorts (Figure). Conclusions: Patients with beta-thalassemia and higher average transfusion burden during the follow-up period had additional HCRU compared with patients who required fewer RBCT units. These data may support physician and payer understanding of the downstream economic impact of RBCT burden in beta-thalassemia. Disclosures Tang: GSK: Consultancy; Roche: Research Funding; Pfizer: Research Funding; Janssen: Research Funding; Amgen: Research Funding. Furnback:Sanofi: Consultancy; Regeneron: Consultancy; Celgene Corporation: Consultancy; Abbott: Consultancy; Astellas: Consultancy; Pfizer: Consultancy; Eli Lilly: Consultancy; Janssen: Consultancy; Johnson & Johnson: Consultancy; Gilead: Consultancy; Novocure: Consultancy; Progentec Diagnostics: Consultancy; Becton Dickinson: Consultancy; AstraZeneca: Consultancy; Bristol-Myers Squibb: Consultancy. Wang:Gilead Sciences: Consultancy, Equity Ownership; Celgene Corporation: Consultancy, Equity Ownership; Regeneron Pharmaceuticals: Consultancy, Equity Ownership; Novocure: Consultancy; Pfizer: Consultancy; Eli Lilly: Consultancy; Johnson & Johnson: Consultancy; Astellas: Consultancy; Amgen, Vertex Pharma, Illumina, Biogen, Alexion Pharma, Incyte, Biomarin Pharma, Seattle Genetics, Sarepta Therapeutics, Array Biopharma, Ionis Pharma, Sage Therapeutics, Mylan NV, Neurocrine Biosciences, Bio Techne Corp, Jazz Pharma, Alnylam Pharma, Blue: Equity Ownership. Tang:Asclepius Analytics: Employment. Huang:Celgene Corporation: Employment. Tang:Celgene Corporation: Employment, Equity Ownership. Musallam:Celgene Corporation: Consultancy.

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Ibrutinib Off-Target Inhibition Inhibits Antibody-Dependent Cellular Phagocytosis but Not Efferocytosis of CLL Cells

Blood ◽

10.1182/blood-2020-139483 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 45-45

Author(s):

Charles C. Chu ◽

Jonathan J. Pinney ◽

Sara K. Blick-Nitko ◽

Andrea M. Baran ◽

Derick R. Peterson ◽

...

Keyword(s):

Drug Concentration ◽

Research Funding ◽

Time Lapse ◽

Publicly Traded ◽

The Past ◽

Btk Inhibitor ◽

Target Molecules ◽

Anti Cd20 ◽

Time Lapse Video ◽

Target Effects

Background Combinations of different targeted therapies, including Bruton tyrosine kinase (BTK) inhibitors and anti-CD20 monoclonal antibodies (mAbs) could improve treatment for CLL. Unexpectedly, the combination of ibrutinib (IBR) with rituximab did not show additional clinical benefit. However, IBR inhibits many off-target molecules that may limit therapeutic mAb clinical effectiveness and a more selective BTK inhibitor, such as acalabrutinib (ACALA), could be more effective in combination with mAb therapy. Initial data from the ELEVATE TN trial support this possibility. IBR off-target effects on antibody-dependent cellular phagocytosis (ADCP), the major mechanism of therapeutic mAb activity could explain this difference. Additionally, IBR induces a higher and longer duration increase in circulating lymphocytes than ACALA. IBR off-target effects on efferocytosis, another phagocytic process involved in apoptotic cell removal, might explain this difference. Methods Using state-of-the-art direct kinetic measurements of phagocytosis by time-lapse video, (Chu et al. J Cell Sci 2020;133:jcs237883) we investigated the effects of IBR and ACALA on phagocytosis (ADCP or efferocytosis) by human monocyte-derived macrophages (hMDM) in vitro. Live cell time-lapse video of 10 μg/ml rituximab (Genentech) mediated ADCP of CLL cells by CellTracker Deep Red (CTDR, Thermofisher) labeled hMDM (20:1 CLL:hMDM cell ratio) either untreated or treated with IBR or ACALA (3-fold serial dilutions from 100 to 0.41 μM) was imaged in a stage-top environmental chamber (37°C and 5% CO2) mounted onto a Nikon Ti-Eclipse inverted microscope with an ELWD 20x/0.45NA S Plan Fluor Ph1 objective and an Andor Zyla 5.5 sCMOS camera. Images were captured sequentially every 4 min over 2.8 h. For each experiment (n = 18), duplicate or triplicate wells for each drug concentration were imaged. For efferocytosis, live cell time-lapse video imaging of phagocytosis of pHrodo iFL Red STP ester (pHrodo Red, Thermo Fisher Scientific) labeled apoptotic CLL cells by CTDR-labeled hMDM (20:1 CLL:hMDM cell ratio) either untreated or treated with IBR or ACALA (2-fold serial dilutions from 10 to 1.25 μM) was collected every 4 min over 2.8 h. For each experiment (n = 7), duplicate or triplicate wells for each drug concentration was imaged and analyzed. Finally, for efferocytosis, the intensity of pHrodo Red dye, a pH-sensitive dye that increases in intensity with acidic pH, as found in the endolysosomes, was measured in the pHrodo Red color channel and analyzed. Results IBR significantly inhibited ADCP at all measured drug concentrations (0.41 μM, p < 0.05; 1.2 μM, p < 0.01; 3.7 - 100 μM, p < 0.001). The mean peak free drug concentration (Cmax) achieved clinically by standard doses for IBR is ~0.5 μM. ACALA only significantly inhibited ADCP at the highest concentration (100 μM, p < 0.001). The Cmax achieved clinically by standard doses for ACALA is ~1.2 μM. ACALA did not inhibit efferocytosis or subsequent transition to endolysosomal compartment at all tested concentrations (p > 0.05). IBR did not inhibit efferocytosis (p > 0.05) and only inhibited transition to endolysosomal compartment at highest concentration tested (10 μM, p < 0.01) Conclusion Our study shows that BTK inhibition does not block ADCP and a more selective BTK inhibitor may prove effective in combination with therapeutic anti-CD20 mAbs. IBR off-target inhibition specifically blocks ADCP and not efferocytosis. Thus, IBR off-target inhibition of ADCP should be via proximal signaling by antibody Fc receptors and not subsequent downstream phagocytic mechanisms in common with efferocytosis. These results also imply the lack of BTK and IBR off-target molecules involvement in efferocytosis. Finally, the increased lymphocytosis seen with IBR compared to ACALA treatment in CLL cannot be explained by IBR off-target effects on efferocytosis. These findings provide a critical understanding of macrophage phagocytosis reduction by BTK inhibitor selectivity that will have important consequences for the development of combination targeted therapies with mAbs. Disclosures Chu: Acerta Pharma/AstraZeneca: Research Funding; Pfizer: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months; TG Therapeutics: Research Funding. Izumi:AstraZeneca: Current equity holder in publicly-traded company; Acerta Pharma: Current equity holder in private company, Ended employment in the past 24 months, Patents & Royalties: Acalabrutinib patents (no royalties). Munugalavadla:Gilead Sciences: Current equity holder in publicly-traded company; AstraZeneca: Current equity holder in publicly-traded company; Acerta Pharma: Current Employment. Barr:Gilead: Consultancy; Morphosys: Consultancy; TG therapeutics: Consultancy, Research Funding; Seattle Genetics: Consultancy; Celgene: Consultancy; AstraZeneca: Consultancy, Research Funding; Janssen: Consultancy; Merck: Consultancy; Genentech: Consultancy; Abbvie/Pharmacyclics: Consultancy, Research Funding; Verastem: Consultancy. VanDerMeid:Acerta Pharma / AstraZeneca: Research Funding. Elliott:Acerta Pharma / AstraZeneca: Research Funding. Zent:Mentrik Biotech: Research Funding; TG Therapeutics, Inc: Research Funding; Acerta / Astra Zeneca: Research Funding.

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Cohort study of healthcare use, costs and diagnoses from onset to 6 months after discharge for takotsubo syndrome in Sweden

BMJ Open ◽

10.1136/bmjopen-2018-027814 ◽

2019 ◽

Vol 9 (2) ◽

pp. e027814 ◽

Cited By ~ 2

Author(s):

Sara Wallström ◽

Inger Ekman ◽

Elmir Omerovic ◽

Kerstin Ulin ◽

Hanna Gyllensten

Keyword(s):

Primary Care ◽

Resource Use ◽

Healthcare Costs ◽

Healthcare Resource ◽

Takotsubo Syndrome ◽

Healthcare Resource Use ◽

Direct Healthcare Costs ◽

The Mean ◽

Discharge From Hospital

ObjectiveLittle is known about the economic impact of takotsubo syndrome (TS) for patients and the health system after initial discharge from hospital. Therefore, the aim of this study was to describe the healthcare resource use and calculate direct healthcare costs for TS, from hospitalisation to 6 months after discharge, and explore the distribution of costs between TS and other diagnoses among patients with TS.Method, participants and settingCohort study investigating direct healthcare costs from hospitalisation, open specialised outpatient and primary care. Healthcare resource use during 6 months after diagnosis with TS was collected for 58 consecutive patients from the Regional Patient Register. Incidence-based direct healthcare costs, in 2015 values, were calculated using diagnosis-related group weights and unit costs from national statistics on healthcare costs.ResultsThe mean length of hospital stay was 10.2 days, index 6.4 and re-admissions 3.8 days. The mean number of follow-up encounters per patient was 15.6, of which two-thirds was specialised outpatient and one-third was primary care. This resulted in an average cost of €10 360. Of this, costs of €8026 (77.5%) occurred during encounters for which at least one of the registered conditions was cardiovascular. Costs differed little according to background characteristics.ConclusionThis study shows that patients utilise hospital, specialised outpatient and primary care after discharge for TS. Most direct healthcare costs relate to cardiac diagnoses. Patients with TS would probably benefit from a supportive follow-up programme after discharge from hospital.

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Effect of Luspatercept on Biomarkers of Erythropoiesis in Patients (Pts) with Lower-Risk Myelodysplastic Syndromes (LR-MDS) in the Medalist Trial

Blood ◽

10.1182/blood-2020-136705 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 38-39

Author(s):

Uwe Platzbecker ◽

Yiming Zhu ◽

Xianwei Ha ◽

Alberto Risueño ◽

Esther Chan ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Reticulocyte Count ◽

Treatment Phase ◽

Fold Increase ◽

Publicly Traded ◽

Advisory Committees ◽

The Past ◽

The Mean ◽

Erythroid Maturation

Introduction: LR-MDS are characterized by ineffective erythropoiesis that leads to anemia and red blood cell (RBC) transfusion dependence. Luspatercept is a first-in-class erythroid maturation agent that binds to select TGF-β superfamily ligands and enhances late-stage erythropoiesis. MEDALIST is a phase 3, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of luspatercept in pts with LR-MDS (IPSS-R-defined Very low-, Low-, and Intermediate-risk) with ring sideroblasts who required RBC transfusions and were ineligible for, intolerant of, or refractory to erythropoiesis-stimulating agents. Clinical benefit (CB; defined as RBC transfusion independence [RBC-TI] ≥ 8 weeks and/or modified hematologic improvement-erythroid [mHI-E] per IWG 2006 criteria) in the primary MEDALIST treatment phase (Weeks 1-24) was achieved by 58.2% of pts in the luspatercept arm and 21.1% in the placebo arm (P < 0.0001). The objective of the study was to investigate the effect of luspatercept treatment on erythropoiesis biomarkers and their relationship to CB in the primary MEDALIST treatment phase (Weeks 1-24). Methods: In the MEDALIST trial, 229 pts were randomized to receive either luspatercept (N = 153) or placebo (N = 76). Reticulocyte count was determined in blood samples collected at baseline and during the primary treatment phase. Serum biomarkers (soluble transferrin receptor 1 [sTfR1], erythroferrone [ERFE], and erythropoietin [EPO]) were measured by ELISA. Bone marrow (BM) erythroid precursors (EP) were determined by cytomorphology from BM aspirates. Biomarker levels were compared between baseline and Week 25 within treatment arms and between pts with CB and without CB in the luspatercept arm using a paired 2-tailed t-test and unpaired t-test (parametric method). Results: In the luspatercept arm, mean reticulocyte count increased from baseline, starting at 8 days after first dose (55.1 vs 34.5 × 109/L at baseline, P < 0.0001), and remained elevated throughout the evaluation period (Figure). Mean EPO levels increased significantly within 6 weeks after first dose (440.1 vs 220.4 IU/L at baseline, P < 0.0001) and remained elevated up to Week 25. Similarly, levels of sTfR1 (P < 0.0001), ERFE (P < 0.0001), and EP (P = 0.0010) were elevated at Week 25 relative to baseline (Table). The mean transfusion burden (within 16 weeks) was significantly reduced at Week 25 compared with baseline (7.2 vs 11.0 units, P < 0.0001). In contrast, in the placebo arm, reticulocyte count, EPO levels, and 16-week transfusion burden remained largely unchanged, while levels of sTfR1 (P < 0.0001), ERFE (P = 0.0431), and EP (P = 0.0010) were significantly lower at Week 25 relative to baseline. In the luspatercept arm, mean baseline EP were higher in 87 pts with CB (31.3%) compared with 63 pts without CB (26.5%; P = 0.0298). No statistically significant differences in baseline EPO, ERFE, sTfR1, reticulocyte count, and 16-week transfusion burden were observed in either group. At Week 25, pts with luspatercept and CB had a significantly greater increase of reticulocyte count (2.7 vs 1.8 mean fold increase from baseline, P = 0.0017), but not EPO levels (2.9 vs 4.3 mean fold increase from baseline, P = 0.1370) compared with pts without CB. Changes in erythropoiesis-related biomarkers (EP, ERFE, and sTfR1) did not differ significantly between pts with and without CB. To investigate whether luspatercept affects erythroid maturation, the ratio of reticulocyte/sTfR1 was calculated. This ratio was reasoned to be an approximation of the ratio of late-stage erythropoiesis (reticulocytes) within total erythropoiesis (sTfR1). Luspatercept increased the mean ratio of reticulocyte/sTfR1 in pts with CB (2.2 in Week 25 vs 1.5 at baseline, P < 0.0001) and no CB (1.9 in week 25 vs 1.3 at baseline, P = 0.0071). Conclusions: Luspatercept-treated pts in the MEDALIST trial had an increase of erythropoiesis-associated biomarkers. Luspatercept-mediated CB (RBC-TI ≥ 8 weeks and/or mHI-E) was associated with increased blood reticulocyte counts and was higher in pts with expanded BM erythropoiesis (as measured by EP) at baseline. Together with the observation that the ratio of reticulocytes/sTfR1 increased during luspatercept treatment, this suggests that the luspatercept mechanism of efficacy in pts with LR-MDS is associated with an increase of erythroid maturation and reticulocytes. Disclosures Platzbecker: Novartis: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Geron: Consultancy, Honoraria; Amgen: Honoraria, Research Funding. Zhu:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Ha:Bristol Myers Squibb: Current Employment. Risueño:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: Named in BMS (before Celgene) patent filings related to predictive patient response biomarkers in hematological malignancies. Chan:Bristol Myers Squibb: Current Employment. Zhang:BMS: Current Employment. Dunshee:Bristol Myers Squibb: Current equity holder in publicly-traded company, Ended employment in the past 24 months; Genentech Inc.: Current Employment, Current equity holder in publicly-traded company. Acar:Bristol Myers Squibb: Ended employment in the past 24 months. Shetty:BMS: Current Employment, Current equity holder in publicly-traded company. Ito:BMS: Current Employment, Current equity holder in publicly-traded company. MacBeth:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Santini:Menarini: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Acceleron: Consultancy; Novartis: Consultancy, Honoraria; Johnson & Johnson: Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Garbowski:Imara: Consultancy; Vifor Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Fenaux:BMS: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Schwickart:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company.

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