Burden of CRAB Events By Relapse in Patients with Newly Diagnosed Multiple Myeloma Not Eligible for Stem Cell Transplant

Abstract Background: For decades, CRAB criteria (hypercalcemia, renal impairment, anemia, and bone disease) have been used to diagnose multiple myeloma (MM), but little is known about the economic burden of CRAB in patients with MM who have relapsed. The only category 1 doublet regimens recommended by NCCN Guidelines for non-transplant candidates are lenalidomide-based (NCCN Myeloma v4.2018). This study aims to evaluate CRAB event rates and the associated economic burden among newly diagnosed MM (NDMM) patients on doublet therapy who were not eligible for stem cell transplant (SCT) and were followed to next line of therapy. Methods: This retrospective study identified patients with ≥ 2 claims of MM (ICD-9-CM code: 203.0x; ICD-10-CM code: C90.0x) ≥ 30 days apart and ≥ 1 treatment (first claim date was used as index date) between January 1, 2011 and December 31, 2015 from the Medicare database. Eligible patients were required to have continuous enrollment from 6 months pre-index or first MM diagnosis date until ≥ 12 months post-index date unless patients died < 12 months post-index date (the follow-up period); ≥ 1 full cycle of therapy; no evidence of prior MM diagnosis or treatment (including autologous SCT [ASCT]); and no evidence of ASCT in the follow-up period. First line of therapy (LOT1) included all treatments prescribed within 60 days of the index date, and patients were included in the doublet therapy cohort based on the index treatment regimen. Progression to a subsequent LOT (LOT2) was defined by the earliest occurrence of an addition or switch to new non-maintenance treatment > 60 days post-index date, restart of any non-maintenance MM treatment after a > 180-day gap, or a dose increase from maintenance to relapse therapy. CRAB event rate per 1,000 person-years (PYs), CRAB event-related healthcare resource utilization (HRU) per patient per month (PPPM), and costs PPPM were evaluated during the LOT1 (the time from index date to end of LOT1) and LOT2 (the time from initiation of LOT2 to end of LOT2) among patients on doublet therapy with LOT1 and those who progressed to LOT2, respectively. Mean was calculated for the continuous variables, while categorical variables were presented as percentage values. Since the LOT2 population was a subset of the LOT1 population and they were not mutually exclusive cohorts, no statistical comparisons were made. Results: The study included 4,970 patients with MM not eligible for ASCT, of which 3,065 (61.7%) patients were prescribed doublet therapy in LOT1. Among these patients on doublet therapy, 1,122 (36.6%) initiated LOT2. The mean age was approximately 77 years, and most patients were white (LOT1, 77.0%; LOT2, 79.7%). The majority of the patients had hypertension (LOT1, 88.3%; LOT2, 86.1%), followed by anemia (LOT1, 79.0%; LOT2, 75.6%) and osteoarthritis (LOT1, 75.7%; LOT2, 76.7%), as comorbidities during the 6 months prior to the index date. CRAB event rates declined from LOT1 to LOT2, with the highest event rate per 1,000 PYs observed for anemia (LOT1, 1,965.1; LOT2, 1,808.2), followed by bone disease (LOT1, 258.1; LOT2, 244.1), renal impairment (LOT1, 167.9; LOT2, 159.9), and hypercalcemia (LOT1, 106.9; LOT2, 99.6); a decline in event rate was observed from LOT1 to LOT2 (Figure 1). CRAB event-related HRU PPPM increased from LOT1 to LOT2, including number of inpatient visits (LOT1, 0.1; LOT2, 0.2), length of inpatient stay (LOT1, 0.8 days; LOT2, 1.0 days), and number of outpatient hospital visits (LOT1, 2.0; LOT2, 2.2). However, the number of outpatient office visits PPPM decreased from LOT1 to LOT2 (LOT1, 0.9; LOT2, 0.8). Similarly, there was a trend toward increased CRAB event-related healthcare costs PPPM from LOT1 to LOT2 (Figure 2) including inpatient (LOT1, USD 1,548; LOT2, USD 2,031), outpatient hospital (LOT1, USD 214; LOT2, USD 301), outpatient office (LOT1, USD 77; LOT2, USD 89), and total medical costs (LOT1, USD 2,120; LOT2, USD 2,593). Conclusions: This study shows that CRAB events were more expensive to treat as patients relapse. Delaying disease progression may be associated with lower HRU and potential cost savings, thereby reducing the burden of MM. A potential limitation of this study is that claims data do not include clinical parameters. Future studies should be considered to evaluate the impact of age and comorbidities on the economic burden associated with CRAB events. This study also highlights the value of delaying progression and the time to next treatment. Disclosures Pandya: Celgene Corporation: Consultancy; STATinMED Research: Employment. Clancy:Celgene Corporation: Employment, Equity Ownership, Research Funding. Shrestha:STATinMED Research: Employment, Equity Ownership. Wang:STATinMED Research: Employment, Equity Ownership.

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Health Care Utilization and Associated Costs in Elderly Persons with Non-CML Myeloproliferative Neoplasms: Real-World Evidence From a United States Medicare Population

Blood ◽

10.1182/blood.v120.21.4273.4273 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4273-4273 ◽

Cited By ~ 1

Author(s):

Sudeep Karve ◽

Gregory L Price ◽

Keith L Davis ◽

Gerhardt M Pohl ◽

Richard A Walgren

Keyword(s):

Health Care ◽

Health Care Utilization ◽

Index Date ◽

Myeloproliferative Neoplasms ◽

Care Utilization ◽

Cell Transplant ◽

Elderly Persons ◽

Employment Equity ◽

Equity Ownership

Abstract Abstract 4273 Background: Non-CML myeloproliferative neoplasms (MPNs), which include essential thrombocythemia (ET), polycythemia vera (PV), myelofibrosis (MF) and MPN not otherwise specified (MPN-NOS), are characterized by activation of JAK2 signaling and abnormal blood cell production. Median survival ranges from months to years for MF and up to a decade or more for PV and ET. Some symptomatic treatment options exist, but with the exception of hematopoietic stem cell transplant, none are curative. Although MPN incidence is highest in persons aged ≥65 years, little is known about overall health care utilization and costs in elderly persons with these diseases. MPNs are more prevalent in the elderly and therefore Medicare enrollees are a highly relevant source for US-based resource utilization and cost data for these diseases. Objective: To compare all-cause health care utilization and costs from four subtypes of elderly MPN patients (ET, PV, MF and MPN-NOS) with matched non-MPN/non-cancer controls. Methods: Retrospective data were taken from the Survey, Epidemiology, and End Results (SEER)-Medicare linked database in the US, which combines clinical information from the SEER cancer registry (MPN reporting has been required since 2001) with medical and pharmacy claims for Medicare enrollees. Patients with a new MPN diagnosis between Jan 1, 2001 and Dec 31, 2007 were selected and evaluated for all-cause health care utilization and costs from Jan 1, 2008 (index date) through Dec 31, 2008 (follow-up end date). Patients were classified by MPN subtype based on the most recent diagnosis information (ICD-O-3 from the SEER registry or ICD-9-CM from Medicare claims) before the index date. Patients who died before follow-up end, had HMO or discontinuous Medicare enrollment during the follow-up year, had enrollment based on end stage renal disease, or a diagnosis of a non-MPN malignancy before follow-up end were excluded from the study. Separate non-MPN/non-cancer control groups were selected for each MPN subtype and matched (5:1) on birth year, gender, ethnicity, geography, and reason for Medicare eligibility. Per patient health care utilization and costs during the follow-up year were aggregated and stratified by care setting. Costs were adjusted to 2010 US$ and represent amounts reimbursed by Medicare to providers. Costs were compared between MPN cases and controls using univariate t-tests. Results: A total of 1,355 MPN patients (n = 445 ET, 684 PV, 81 MF, 145 MPN-NOS) were identified for study inclusion and assigned matching controls. For ET, PV, MF and MPN-NOS cases, respectively, mean [SD] age at index was 75.5 [9.7], 70.8 [11.3], 70.8 [10.4] and 74.1 [8.9] years and % female was 69.0, 43.9, 54.3, and 55.2. Mean [SD] years between first MPN diagnosis and study index date was 3.1 [2.0], 3.4[1.9], 2.7 [2.0], and 3.1 [2.1] for ET, PV, MF and MPN-NOS cases, respectively. A significantly (p<0.05) higher proportion of MPN cases, regardless of subtype, had ≥1 hospitalization during follow-up vs. controls (ET vs. control: 22% vs. 16%, PV vs. control: 27% vs. 15%, MF vs. control: 31% vs. 12%, MPN-NOS vs. control: 36% vs. 17%). Mean [SD] total days of hospital care were similarly higher in MPN cases (ET vs. control: 2.7 [12.8] vs. 1.6 [6.6], PV vs. control: 2.6 [7.0] vs. 1.7 [9.5], MF vs. control: 2.5 [6.2] vs. 1.2 [5.9], MPN-NOS vs. control: 4.0 [10.0] vs. 2.1 [13.7]), although the PV vs. control difference was not statistically significant. The ER visit rate during follow-up was also significantly (p<0.05) higher in MPN cases (ET vs. control: 34% vs. 24%, PV vs. control: 38% vs. 25%, MF vs. control: 46% vs. 21%, MPN-NOS vs. control: 44% vs. 29%). All-cause costs for MPN cases vs. matched controls are presented in the figure. Mean total costs per patient, driven equally by inpatient and outpatient services, were significantly (p<0.001) higher in MPN cases (ET vs. control: $11,259 vs. $8,897, PV vs. control: $13,337 vs. $8,530, MF vs. control: $20,917 vs. $7,367, MPN-NOS vs. control: $20,174 vs. $9,800). Conclusions: Total health care costs during a given year for elderly patients with MPNs are 1.3 to 3 times higher (depending on subtype) than those of matched controls. These findings may help inform future cost effectiveness evaluations of novel MPN treatments, as well as decision making in the provision of optimal MPN care within a Medicare system in which resources are finite and must be allocated ethically and efficiently. Disclosures: Karve: RTI Health Solutions: Consultancy, Research Funding. Price:Eli Lilly and Company: Employment, Equity Ownership. Davis:Eli Lilly, Merck, GlaxoSmithKline, Bristol-Myers Squibb, Pfizer, Eisai, Sanof-Aventis, Gilead Sciences, MedImmune: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Pohl:Eli Lilly and Company: Employment, Equity Ownership. Walgren:Eli Lilly and Company: Employment, Equity Ownership.

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Real world treatment patterns in chronic myeloid leukemia patients newly initiated on tyrosine kinase inhibitors in an U.S. integrated healthcare system

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155217697484 ◽

2017 ◽

Vol 24 (4) ◽

pp. 253-263

Author(s):

Nazia Rashid ◽

Han A Koh ◽

Kathy J Lin ◽

Brian Stwalley ◽

Eugene Felber

Keyword(s):

Chronic Myelogenous Leukemia ◽

Index Date ◽

Stem Cell Transplant ◽

Study Time ◽

Myelogenous Leukemia ◽

Prior History ◽

Cell Transplant ◽

Time Period ◽

History Of

Purpose To evaluate treatment patterns in patients diagnosed with incident chronic myelogenous leukemia (CML) newly initiating therapy with imatinib, dasatinib, or nilotinib. Patients were followed to determine switching and discontinuation rates. Factors associated with switching or discontinuation from index TKI therapy, reasons for discontinuation based on electronic chart notes, and frequency of laboratory monitoring were assessed during the follow-up period. Methods A retrospective cohort study was conducted in chronic myelogenous leukemia patients aged ≥ 18 years who were identified from the Kaiser Permanente Southern California (KPSC) Cancer Registry database during the study time period of 1 January 2007 to 12 December 2013. The index date was defined as the date of the first TKI prescription (imatinib, dasatinib, or nilotinib) identified during the study time period with no prior history of TKI use within 12 months. Patients had to have continuous membership with drug benefit eligibility and no prior history of stem cell transplant (SCT) or other cancers during the 12 months prior to the index date. Baseline characteristics were identified during 12 months prior to the index date and outcomes were identified during the follow-up period after the index date. All patients were followed from index TKI therapy until end of study time period (12 December 2014), death, stem cell transplant, or disenrollment from the health plan unless one of the following occurred first: a patient switched their index therapy, or a patient discontinued their index therapy. Forward stepwise selection multivariable logistic regression models were used to evaluate factors associated with patients who continued therapy compared to those who switched or discontinued therapy with the index TKI. Chart notes were reviewed 30 days prior and 30 days post index TKI discontinuation to evaluate reasons for discontinuation. Molecular and cytogenetic testing frequency was also assessed during the follow-up period among the different patient groups. Results Two hundred sixteen patients were identified with incident chronic myelogenous leukemia and use of TKI therapy: 189 (87.5%) received imatinib, 19 (8.8%) received dasatinib, and 8 (3.7%) received nilotinib. The mean age on index date was 53 years and 63% were male; 103 patients (48%) continued on their index therapy, while 62 patients (28%) switched, and 51 patients (24%) discontinued.

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The Economic Burden of Pleural Effusions (PE) In Patients with Chronic Myeloid Leukemia (CML).

Blood ◽

10.1182/blood.v116.21.3841.3841 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3841-3841

Author(s):

Eric Qiong Wu ◽

Annie Guerin ◽

Vamsi Bollu ◽

Denise Williams ◽

Amy Guo ◽

...

Keyword(s):

Resource Utilization ◽

Medical Cost ◽

Economic Burden ◽

Regression Models ◽

Index Date ◽

Healthcare Resource ◽

Healthcare Resource Utilization ◽

Total Medical Cost ◽

Employment Equity ◽

Equity Ownership

Abstract Abstract 3841 Background: Ph+ CML patients may develop PE, as an adverse event of some tyrosine kinase inhibitors (TKI) drug therapy. PE is characterized by an excessive accumulation of fluid in the fluid-filled space that surrounds the lungs. PE requires medical care, may compromise the course of CML treatment, and have economic consequence beyond the costs of treating PE. Aim: To compare healthcare resource utilization and costs between CML patients treated with a TKI who developed PE and their matched PE-free controls. Methods: MarketScan and Ingenix Impact databases (2001-2009) were combined to identify adult CML patients (ICD-9CM code 205.1×) who received ≥1 prescription of imatinib, dasatinib, or nilotinib before the index date and had continuous enrollment ≥6 months prior to and after the index date. The index date was defined as 30 days before the first PE diagnosis (ICD-9CM code 511.9×) for patients with PE and was randomly selected among all the eligible calendar dates (i.e., following a prescription for a TKI and a diagnosis for CML) for the PE-free controls. Patients were followed for 6 months after the index date. PE and PE-free patients were matched on a 1:1 ratio using propensity score matching. PE-related (i.e., medical claims with a PE diagnosis) resource utilization (inpatient [IP], outpatient [OP], emergency room [ER] and other medical visits) and costs were estimated for PE patients. To estimate the overall incremental impact of PE, all-cause and CML-related (i.e., medical services associated with a diagnosis code of 205.1×) resource utilization and costs were compared between PE and PE-free controls. All costs were reported in 2009 US dollars. Incidence rate ratios (IRR) for healthcare resource utilization were estimated by Poisson regression models. Incremental costs were estimated using generalized linear models or two-part models. Multivariate regression models controlled for age, gender, treatment duration with tyrosine kinase inhibitor, other chemotherapy, bone marrow or stem cell transplant, CML complexity, Charlson comorbidity index, adverse events, and comorbidities. Results: The study included 179 matched pairs. On average, patients were 63.4 and 63.8 years old with 41% and 49% of the population being female for PE-free and PE patients, respectively. During the study period, PE patients were estimated to have an average of 0.62 PE-related IP admissions, 8.43 IP days, 0.06 ER admissions, and 1.76 OP visits. Compared to PE-free patients, PE patients had more than 7 times as many IP days (IRR=7.23; p<.01), almost 3 times as many IP admissions (IRR=2.96; p<0.01), almost twice as many OP visits (IRR=1.98; p<.01) and ER visits (IRR=1.77; p<.01). Especially, PE patients had almost 10 times as many CML-related IP days (IRR=9.91; p<.01), more than 3 times as many CML-related IP admissions (IRR=3.95; p<0.01), twice as many CML-related OP visits (IRR=2.16; p<.01), and almost 6 times as many CML-related ER visits (IRR=5.60; p<.01). On average, PE-related medical costs were estimated at $11,015 per patient, where 84.2% was accounted for by IP costs. Total costs for all-cause related medical services were estimated at $37,566 for PE patients and $14,841 for PE-free patients. After adjusting for confounding factors, the incremental total medical cost of PE patients was $22,299 (p<.01), mostly due to the incremental OP cost ($12,931; p<.01) and IP cost ($8,737; p<.01). Similarly, PE patients incurred higher CML-related medical costs compared to PE-free patients, with a $15,859 (p<.01) incremental cost. Conclusion: Compared to PE-free patients, PE patients have a substantial economic burden with higher PE-related costs, CML-related costs, and total medical cost. Disclosures: Wu: Analysis Group, Inc.: Employment. Guerin:Analysis Group, Inc.: Employment. Bollu:Novartis: Employment, Equity Ownership. Williams:Novartis: Employment, Equity Ownership. Guo:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Ponce de Leon Barido:Analysis Group, Inc.: Employment. Yu:Analysis Group, Inc.: Employment.

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Treatment Sequencing Patterns in Medicare-Enrolled Patients with Multiple Myeloma

Blood ◽

10.1182/blood.v128.22.2120.2120 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2120-2120 ◽

Cited By ~ 1

Author(s):

Shuling Li ◽

Tanya Natwick ◽

Akeem Yusuf ◽

Irena Sarah Vidito ◽

Khalid Mezzi ◽

...

Keyword(s):

Multiple Myeloma ◽

Index Date ◽

Employment Equity ◽

Drug Regimens ◽

Medicare Patients ◽

Equity Ownership ◽

Treatment Sequencing ◽

Line Of Therapy ◽

The Impact ◽

Treatment Sequences

Abstract Introduction: Over the last decade, several novel therapies have been approved for multiple myeloma (MM) leading to significant improvement in the prognosis of MM patients. MM patients are often treated with multiple lines of therapy as relapse occurs. With the numerous options of therapeutic agents and novel combinations of regimens, the treatment for MM has become more complicated. However, little is known regarding the treatment sequencing patterns for Medicare patients with MM. In this study, we described the use of drug regimens by lines of therapy and characterized treatment sequences in Medicare patients with MM. Methods: Using a validated algorithm (Princic et al. Blood 2015;126:4521), we identified adult MM patients (≥ 18 years old) in 2008-2011 from the Centers for Medicare & Medicaid Services 100% Hematologic Cancer file (2007-2012) who began first-line (1L) treatment. Patients who advanced to second-line (2L), third-line (3L), and fourth-line (4L) were identified if a 90 day gap in all treatments was observed or when a drug was added to a regimen >90 days after the line index date. Drug regimens were based on National Comprehensive Cancer Network MM treatment guidelines and were identified using National Drug Code and Healthcare Common Procedure Coding System codes. Patients were included in the study if they received monotherapy, doublets, or triplets at 1L. The study period was from the 1L initiation date to the earliest of death, disenrollment from Medicare Parts A, B, and D coverage, receipt of treatments other than the above-mentioned drug regimens, or December, 31, 2012. We described the distribution of type of drug regimens by lines of therapy, overall and by age defined at MM index date, and characterized treatment sequencing patterns for patients who advanced to 2L, 3L, and 4L by type of drug regimens in the prior line of therapy, respectively. Results: In total, 12563 MM patients initiated 1L therapy. Of these, 9% were aged 18-64 years (enrolled in Medicare due to disabilities), 42% aged 65-74 years, and 49% aged ≥ 75 years. Most patients were white (78%) and more than half were female (53%). We identified 5647 (45%), 2243 (18%), and 773 (6%) patients who advanced to 2L, 3L, and 4L, respectively. Overall, doublets were the most common 1L regimen (62%), followed by monotherapy (21%) and triplets (17%). Most common treatments for monotherapy in 1L were dexamethasone (52%), lenalidomide (21%), and bortezomib (17%). The pattern was similar among patients who advanced to a 2L, 3L, or 4L, respectively, though more triplets were used at advanced lines. For 1L therapy, only 12% of patients aged ≥ 75 years received triplets, in contrast to >20% of triplet use in 3L and 4L respectively (Table). Of patients who received monotherapy in 1L and advanced to 2L, 37% continued monotherapy and 63% switched to more dense regimens (doublets, 53%; triplets 10%). Of patients who received doublets in 1L and advanced to 2L, 58% continued doublets, 22% switched to triplets, and 20% to monotherapy. Of patients who received triplets in 1L and advanced to 2L, 26% continued triplets and 74% switched to less dense regimens (doublets, 47%; monotherapy, 27%). Treatment sequencing patterns were similar for patients who advanced to 3L and 4L with monotherapy or doublets in prior lines, while the proportion of patients who repeated triplets increased to about 32% in 3L and 37% in 4L (Figure). Conclusions: Among Medicare patients with MM, doublets were the most frequently used regimens across all lines of therapy, while triplets were used in more advanced lines. Patients on monotherapy or doublets were more likely to retain their treatment pattern when they advance to the next line of therapy, while those on triplet regimen were more likely to switch to a less dense regimen when they advance to their next line of therapy. Fewer patients of older age (75+ years) were prescribed triplet therapies, however triplet use in this patient group increases in more advanced lines. These results provide a baseline description of treatment patterns from which we will be able to benchmark the impact of the recent introduction of novel agents and their use in elderly MM patients. Further studies assessing the comparative effectiveness and benefit-risk of treatment sequences are warranted. Figure Figure. Disclosures Yusuf: Amgen Inc.: Employment, Equity Ownership. Vidito:Amgen Inc.: Employment, Equity Ownership. Mezzi:Amgen Inc.: Employment, Equity Ownership. Werther:Amgen Inc.: Employment, Equity Ownership.

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Eculizumab Prevents Thrombotic Microangiopathy: Long-Term Follow-up Study of Patients with Atypical Hemolytic Uremic Syndrome

Blood ◽

10.1182/blood.v126.23.2252.2252 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2252-2252 ◽

Cited By ~ 1

Author(s):

Laurence A. Greenbaum ◽

Yahsou Delmas ◽

Fadi Fakhouri ◽

John F. Kincaid ◽

Christoph Licht ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Atypical Hemolytic Uremic Syndrome ◽

Employment Equity ◽

Advisory Committees ◽

Long Term Follow Up ◽

Uremic Syndrome ◽

Equity Ownership ◽

Event Rates

Abstract Background: Eculizumab was demonstrated to effectively treat and prevent thrombotic microangiopathy (TMA) and to improve renal function and hematologic parameters for up to 2 years in4 previous prospective clinical trials and in 1 retrospective study of patients with atypical hemolytic uremic syndrome (aHUS). Patients in these studies enrolled in a long-term follow-up study, in which rates of TMA were evaluated during eculizumab treatment and during discontinuation from eculizumab. Methods: Data were gathered from an ongoing, observational, multicenter study of aHUS patients treated with eculizumab in 5 prior clinical studies. The primary endpoint was TMA event rate post-parent study during on-treatment (ON; among patients receiving eculizumab) and off-treatment (OFF; among patients who discontinued eculizumab) periods. Results: As of March 28, 2015, 87 patients, including 35 children <18 years of age (40%) and 52 adults ≥18 years of age (60%), enrolled in the study (Table). Of these, 76 patients had ON and 39 patients had OFF treatment periods with median follow-up of 26.1 and 20.1 months, respectively. A reduced dosage of eculizumab was received by 33 of 87 patients (38%). Seventeen of 39 patients (44%) reinitiated eculizumab after therapy discontinuation. The TMA event rates were 7.3 and 19.9 per 100 patient-years for ON and OFF patients, respectively. The rate of TMA in ON patients was greater in those receiving reduced dosing compared with label recommendations (Table). OFF patients had higher estimated glomerular filtration rates at time of discontinuation than ON patients. Age, frequencies of higher-risk complement factor mutations (CFH, C3, or CFB) and kidney transplant status were not different between ON and OFF patients. Factors that independently predicted TMA events included: ON treatment status (compared with OFF; hazard ratio [HR], 0.19; 95% confidence interval [CI], 0.07‒0.49; P<0.001), higher-risk mutations (compared with no mutation; HR, 5.51; 95% CI, 1.61‒18.84; P=0.007), and lower-risk mutations (compared with no mutation; HR, 3.70; 95% CI, 1.05‒13.02; P=0.04). Conclusions: The TMA event rate was 2.7-fold higher after eculizumab discontinuation compared with patients receiving ongoing eculizumab therapy. TMA event rates were lowest during on-label dosing, higher during reduced dosing, and highest during off-treatment periods. These findings suggest that patients with aHUS have a progressive increase in the risk of TMA events during periods of reduced dosing and after discontinuation of eculizumab, compared with on-label eculizumab dosing. Disclosures Greenbaum: Alexion Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Fakhouri:Alexion Pharmaceuticals: Consultancy. Kincaid:Alexion Pharmaceuticals: Employment, Equity Ownership. Licht:Alexion Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Achillon: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Mix:Alexion Pharmaceuticals: Employment, Equity Ownership. Provôt:Alexion Pharmaceuticals: Honoraria. Rondeau:Alexion Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sheerin:Alexion Pharmaceuticals: Honoraria. Wang:Alexion Pharmaceuticals: Employment, Equity Ownership. Menne:Alexion Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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Real-World Differences in Characteristics and Survival of Relapsed AML Patients with and without Transplant

Blood ◽

10.1182/blood-2018-99-118621 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2297-2297

Author(s):

Abdalla Aly ◽

Saurabh Ray ◽

Anuj Shah ◽

Marc Botteman

Keyword(s):

Overall Survival ◽

Real World ◽

Research Funding ◽

Cell Transplant ◽

Employment Equity ◽

Risk Of Death ◽

Hazard Ratios ◽

Equity Ownership ◽

To Receive

Abstract Background: Some AML patients, particularly those relapsing rapidly, may not get a chance to receive a potentially curative stem cell transplant (SCT) due to early death, among other reasons. This study compares the differences in characteristics and survival of relapsed AML patients with and without SCT, as observed in a real-world setting. Methods: Relapsed AML patients aged 66-75 years were identified from the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database by medical claims associated with ICD-9 code 205.02 (2009-2014). Patients were followed from relapse to the earliest of death, SCT, or end of follow-up. Baseline characteristics were compared between relapsed AML patients with and without SCT. The SCT rates were estimated after adjusting for the competing risk of death. The Fine and Gray method was used to identify predictors of receiving SCT and were reported in terms of sub-distribution hazard ratios (SHR) and 95% confidence intervals (CI). Kaplan-Meier estimates (reported in terms of median and 6-, 12-, and 24-months survival rates, tested with a log Rank test statistic) and a Cox proportional hazards model adjusting for age, sex, race, Census region, marital status, urban location, Charlson comorbidity index (CCI), and diagnosis year (reported in terms of hazard ratios (HR) and 95% CI) was used to assess the difference in survival between patients with and without SCT. Results: Of the 474 relapsed AML patients (median age, 70 years, median follow up, 4.4 months, male, 55%) included in the study, 8% received SCT, 80% died without having SCT and 12% were administratively censored. Patients were less likely to receive SCT if they were 71-75 years old (SHR 0.28, 95% CI (0.19 to 0.41; P <.001) and had higher comorbidity with CCI >3 (SHR 0.16, 95% CI (0.06 to 0.44; P <.001). The median overall survival was 16.1 months for patients with SCT vs. 4.1 months for those without SCT (log rank P <.001; adjusted HR 0.52, 95% CI (047 - 0.57; P <.001)). The 6-, 12-, and 24-month overall survival for all relapsed AML patients was 42%, 26%, and 12%, respectively. For patients with SCT, the 6-, 12-, and 24-month overall survival was 84%, 59%, and 43%, respectively. For patients without SCT, the 6-, 12-, and 24-month overall survival was 39%, 23%, and 12%, respectively. Conclusions: Relapsed AML patients who received SCT experienced significantly longer survival compared to those who did not receive SCT in this elderly study population. However, only 8% of all relapsed AML patients received SCT. Therapies that bridge more patients to SCT are expected to improve overall survival in this high unmet need population. Disclosures Aly: AstraZeneca: Research Funding; Celgene: Research Funding; BMS: Research Funding; Pharmerit International: Employment, Research Funding; Daiichi Sankyo Incorporated: Research Funding. Ray:Daiichi Sankyo Incorporated: Employment, Equity Ownership. Shah:Celgene: Research Funding; Pharmerit International: Employment, Research Funding; Daiichi Sankyo Incorporated: Research Funding; BMS: Research Funding. Botteman:Daiichi Sankyo Incorporated: Research Funding; BMS: Research Funding; Celgene: Research Funding; Pharmerit International: Employment, Equity Ownership, Research Funding; Bioverativ: Consultancy, Other: Provided consulting to Bioverativ, Research Funding.

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Association Between Age and Bleeding Events of Different Severities Among Patients with Nonvalvular Atrial Fibrillation in a Managed Care Population

Blood ◽

10.1182/blood.v120.21.4238.4238 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4238-4238

Author(s):

Steven Deitelzweig ◽

Brett Pinsky ◽

Erin Buysman ◽

Michael Lacey ◽

Yonghua Jing ◽

...

Keyword(s):

Atrial Fibrillation ◽

Emergency Department ◽

Older Patients ◽

Claims Data ◽

Bleeding Events ◽

Nonvalvular Atrial Fibrillation ◽

Employment Equity ◽

Equity Ownership ◽

Event Rates

Abstract Abstract 4238 Background: Risk of bleeding is an important consideration among patients with nonvalvular atrial fibrillation (NVAF) due to the need for stroke prevention through anticoagulation. Older patients may be at risk for more frequent or more severe bleeding events. Objective: To describe the incidence of bleeding events in various age groups of patients with NVAF. Methods: Administrative claims data were used for this retrospective study. Adults with healthcare claims data related to atrial fibrillation (ICD-9-CM 427.31) between Jan 2005 and Jun 2009 but no evidence of valvular disease were included. Patients were followed until the earliest of death, disenrollment from the health plan, or 30 Jun 2010. Bleeding events in the follow-up period were categorized as major, serious non-major, or minor. A bleeding event was considered major if it was associated with any of the following: inpatient care, blood transfusion, decreased hemoglobin or hematocrit, physician guided medical or surgical treatment, intracranial bleed, or death. Serious non-major events were those involving vascular injury or critical site bleeding and were associated with outpatient hospital care or an emergency department visit. Minor bleeds were those associated with noncritical anatomical sites and an emergency department, outpatient hospital, or office visit. Patients were grouped based on their age as of the first atrial fibrillation diagnosis: younger than 65 years or 65 years and older; bleeding events in the subgroup of patients aged 75 years and older were also examined. Results: The mean (SD) age of the study sample (N=48,260) was 67 (13) years and 62.2% of the patients were male. Mean (SD) follow-up duration was 802 (540) days (median 673 days). Event rates for major bleeds were 5.2 events per 100 patient-years for patients aged younger than 65 years and 13.9 major bleeds per 100 patient-years for patients aged 65 years and older. Patients aged 75 and older had 15.6 major bleeds per 100 patient-years. Approximately 38.9% of all bleeding events experienced by patients aged 65 years and older were major. Approximately 23.3%, 33.6%, and 35.8% of major bleeds among patients younger than 65 years, 65 years and older, and 75 years and older, respectively, were associated with a hospitalization. Corresponding event rates for incident bleeds associated with an inpatient stay were 4.7 bleeding events per 100 patient-years for patients aged younger than 65 years, 12.0 events per 100 patient-years for patients aged 65 years and older, and 13.6 events per 100 patient-years for patients aged 75 years and older. Conclusions: Increasing age was associated with increased rate of any type of bleeding. The increase in rate with increasing age was particularly notable for major bleeds. Disclosures: Deitelzweig: Bristol-Myers Squibb/OptumInsight: Research Funding, Speakers Bureau. Pinsky:OptumInsight: Employment. Buysman:OptumInsight: Employment. Lacey:OptumInsight: Employment. Jing:Bristol-Myers Squibb: Employment, Equity Ownership. Wiederkehr:Pfizer: Employment, Equity Ownership. Graham:Bristol-Myers Squibb: Employment, Equity Ownership.

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Economic Burden of Acute Graft-Versus-Host Disease (GvHD) Following Allogeneic Hematopoietic Cell Transplant (HCT) for Hematologic Malignancies

Blood ◽

10.1182/blood.v128.22.1187.1187 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1187-1187 ◽

Cited By ~ 3

Author(s):

Walter W Grubb ◽

Samuel Huse ◽

Naufil Alam ◽

Samuel Dychter ◽

John R. Wingard ◽

...

Keyword(s):

Economic Burden ◽

Healthcare Costs ◽

Acute Gvhd ◽

Hematologic Malignancies ◽

Index Admission ◽

Employment Equity ◽

Allogeneic Hct ◽

Equity Ownership ◽

One Year

Abstract Background: Allogeneic HCT is a potentially curative procedure for many hematologic malignancies, but is associated with several complications. Acute GvHD is a condition that affects 35-50% of allogeneic HCT recipients, typically occurs within 100 days after transplant, and can be life-threatening. Existing treatments are poorly tolerated and frequently ineffective. While the clinical consequences of acute GvHD are understood, the economic burden of the condition has not been well characterized. Methods: Using a large US healthcare claims database (Truven MarketScan® Commercial Claims and Encounters Database), patients aged ≥2 years old were identified who underwent allogeneic HCT between October 2009 and March 2013. Patients without continuous health plan enrollment or evidence of hematologic malignancy in the 6-month period prior to the "Index Admission" (hospital admission during which HCT was performed) were excluded. Patients were followed from the first day of the Index Admission until death, plan disenrollment, or one year; whichever occurred first ("Follow-Up"). Patients were classified into two cohorts: "Acute GvHD" based on ICD-9 CM diagnosis codes within first 100 days of Follow Up, or "No Acute GvHD". Total healthcare costs (inpatient care, outpatient care, outpatient pharmacy) and hospital length of stay (LOS) at discharge from Index Admission, the 100th day of Follow-Up, and the 365th day of Follow-Up were determined. Reimbursed amounts (plan payment plus patient liability) were used as a proxy for healthcare costs. Total healthcare costs and LOS between the two cohorts were compared for each of the three evaluation periods using Student's t-tests (unadjusted analyses), and analyses of covariance (ANCOVA; adjusting for differences in age, sex, plan type, geography, year of Index Admission, type of malignancy, Charlson Comorbidity Index score, and pre-admission healthcare cost). Results: 1,635 patients underwent HCT and met all selection criteria (mean age was 48 years, 56% were men, acute myeloid leukemia was the most common malignancy); 42% met the criteria for inclusion in the Acute GvHD cohort. Univariate mean total healthcare costs for the Acute GvHD cohort (vs No Acute GvHD) were $36,651 greater during Index Admission, $83,322 greater at the 100th day of Follow-Up, and $123,220 greater at the end of the 1-year Follow-Up (all p<0.01); additional mean LOS (days) were 5.7 during Index Admission, 14.0 at the 100th day of Follow-Up, and 17.4 at the end of the 1-year Follow-Up (all p<0.01) [Table 1]. Multivariate-adjusted mean total healthcare costs were $24,292 greater during Index Admission (p=0.02), $73,622 greater at the 100th day of Follow-Up (p<0.01), and $114,698 greater at the end of the 1-year Follow-Up (p<0.01); additional LOS was 5.2 during the Index Admission, 14.1 at the end of the 100th day of Follow-Up, and 17.9 at the end of the 1-year Follow-Up (all p<0.01) [Table 2]. Conclusions: Over the one-year period following allogeneic HCT, patients who develop Acute GvHD experience over $100,000 more in total healthcare costs-and nearly three additional weeks in hospital-relative to those who do not. While healthcare claims appear to represent a good source with which to assess the impact of complications of HCT, confirmation with prospective clinical studies is recommended. Given that nearly one-half of patients develop Acute GvHD, our findings suggest that therapeutic strategies that prevent this complication may confer substantial savings to the healthcare system. Disclosures Grubb: Fate Therapeutics: Employment, Equity Ownership. Huse:Evidera: Employment; Fate Therapeutics: Consultancy. Alam:Evidera: Employment; Fate Therapeutics: Consultancy. Dychter:Fate Therapeutics: Employment, Equity Ownership. Wingard:Merck: Consultancy; Ansun: Consultancy; Fate Therapeutics: Consultancy; Gilead: Consultancy; Astellas: Consultancy. Berger:Evidera: Employment; Fate Therapeutics: Consultancy.

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Overall Survival, Adverse Events, and Economic Burden in Medicare-Insured Patients with Mantle Cell Lymphoma Receiving Cancer-Directed Therapy

Blood ◽

10.1182/blood-2019-122841 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 63-63

Author(s):

Shaum M Kabadi ◽

Ravi K Goyal ◽

Saurabh P Nagar ◽

Keith L Davis ◽

Hannah Le ◽

...

Keyword(s):

Economic Burden ◽

Systemic Therapy ◽

Research Funding ◽

Index Date ◽

Treatment Initiation ◽

Cell Lymphoma ◽

Baseline Period ◽

Mantle Cell ◽

Equity Ownership ◽

Line Of Therapy

Background: Most data on overall survival (OS) and adverse events (AEs) in patients with mantle cell lymphoma (MCL) are from controlled trials in academic centers; data from real world management and outcomes in patients with MCL are sparse. We therefore conducted a population-based retrospective cohort study of patients with MCL in the Medicare database to assess treatment patterns, OS, AEs, and economic burden. Methods: Patients with MCL who received any systemic cancer-directed treatment from 2013 to 2015 were selected from the nationwide Medicare claims database and followed through 2016. The date of the first observed systemic therapy defined each patient's index date. Patients were included if they (a) were ≥ 18 years of age at the index date; (b) had ≥ 12 months of continuous Medicare enrollment before the index date (baseline period); and (c) had no evidence of prior MCL-directed treatment (systemic therapy and/or SCT) at any time before the index date (i.e., during at least the previous 12 months). An observed line of therapy was defined as all agents received on or within 35 days after the first claim for a systemic therapy drug; the observed therapy line was considered ended upon switch to another regimen or a gap ≥ 90 days after the last treatment. OS was estimated by the Kaplan-Meier method from the index date (start of first observed line of therapy) until the last follow-up or death. We also calculated rates of occurrence for hematologic and nonhematologic AEs often associated with the most commonly observed regimens (irrespective of observed line of therapy). The occurrence of AEs was defined based on the presence of at least one claim containing an AE-specific diagnosis code during the treatment, regardless of any history of the AE before treatment initiation. All-cause health care costs were assessed from Medicare's perspective. Multivariable models were fitted to assess the association between number of AEs and average costs during the first observed therapy. Results: We analyzed 1,465 patients who met the inclusion criteria (median age=74 years; 68% male; 93% white). Across all observed lines of therapy, ibrutinib monotherapy (Ibr) (n=588 [40%]) was the most frequently used regimen, followed by bendamustine/rituximab (BR) (n=527 [36%]). Ibr recipients had a median age of 75 years, median Charlson Comorbidity Index (CCI) score of 4.0, and were followed for a median duration of 15 months; 52% died during the study period. BR recipients had a median age of 75 years, median CCI score of 3.0, and were followed for a median duration of 21 months; 28% died during the study period. In Ibr recipients, median OS was 22 months (95% CI = 16.9-28.6) and 24-month OS was 47% (95% CI = 42.9%-50.5%). In BR recipients, median OS was not reached while OS at 24 months was 73% (95% CI = 69.4%-76.0%). The occurrence of common AEs during Ibr and BR therapies are presented in Tables 1 and 2. The average per patient per month costs, among all patients, were $2,501 (SD = $2,818) during the baseline period and $12,604 (SD = $14,437) during the period after initiation of the first observed MCL-directed systemic therapy. Multivariable analysis showed that the patients with 3 or more AEs had nearly 4 times higher monthly per patient costs (cost ratio = 4.12, 95% CI = 3.53-4.82) compared with those with 0-2 AEs. Conclusions: Two-year survival rates observed in this study are comparable to those reported in clinical trials (47% for Ibr in the relapsed disease setting [Wang, 2015, Blood]) and nearly 75% for BR in patients with relapsed indolent disease and MCL [Rummel, 2016, Lancet]). Rates of AE occurrence in Ibr- and BR-treated patients in this study highlight the substantial burden and susceptibility to AEs among Medicare patients in the real-world setting. These findings also demonstrate a substantial increase in the economic burden from the baseline period to the period after MCL treatment initiation and as the number of AEs increased. Disclosures Kabadi: AstraZeneca: Employment, Equity Ownership. Goyal:RTI Health Solutions: Employment. Nagar:RTI Health Solutions: Employment. Davis:RTI Health Solutions: Employment. Le:AstraZeneca: Employment, Other: Stocks. Wang:Dava Oncology: Honoraria; Guidepoint Global: Consultancy; BioInvent: Consultancy, Research Funding; VelosBio: Research Funding; Loxo Oncology: Research Funding; Celgene: Honoraria, Research Funding; Juno Therapeutics: Research Funding; Aviara: Research Funding; Kite Pharma: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics: Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; MoreHealth: Consultancy, Equity Ownership; Acerta Pharma: Consultancy, Research Funding. Kaye:RTI Health Solutions: Employment.

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Comorbidity Burden in Elderly Persons with Non-CML Myeloproliferative Neoplasms: Real-World Evidence From a United States Medicare Population

Blood ◽

10.1182/blood.v120.21.1734.1734 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1734-1734

Author(s):

Keith L Davis ◽

Gregory L Price ◽

Sudeep Karve ◽

Gerhardt M Pohl ◽

Richard A Walgren

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Renal Disease ◽

Index Date ◽

Myeloproliferative Neoplasms ◽

Cost Of Care ◽

Employment Equity ◽

Comorbidity Burden ◽

Equity Ownership

Abstract Abstract 1734 Background: Non-CML myeloproliferative neoplasms (MPNs), which include essential thrombocythemia (ET), polycythemia vera (PV), myelofibrosis (MF) and MPN not otherwise specified (MPN-NOS), are characterized by activation of JAK2 signaling and abnormal blood cell production. MPN patients, especially those aged ≥65 years (in whom MPN incidence is highest), are at increased risk for cardiovascular and other comorbidities (Vannucchi et al. Blood 2007;110:840-6, Marchioli et al. J Clin Oncol 2005;23:2224-32). However, comorbidity rates in elderly MPN patients as compared with non-MPN controls have not been described in previous literature. MPNs are more prevalent in the elderly and therefore Medicare enrollees are a highly relevant source for US-based epidemiological data for these diseases. Objective: To compare comorbidity rates from four subtypes of elderly MPN patients (ET, PV, MF and MPN-NOS) with matched non-MPN/non-cancer controls. Methods: Retrospective data were taken from the Survey, Epidemiology, and End Results (SEER)-Medicare linked database in the US, which combines clinical information from the SEER cancer registry (MPN reporting has been required since 2001) with medical and pharmacy claims for Medicare enrollees. Patients with a new MPN diagnosis between Jan 1, 2001 and Dec 31, 2007 were selected and evaluated for comorbidities from Jan 1, 2008 (index date) through Dec 31, 2008 (follow-up end date). Patients were classified by MPN subtype based on the most recent diagnosis information (ICD-O-3 from the SEER registry or ICD-9-CM from Medicare claims) before the index date. Patients who died before follow-up end, had HMO or discontinuous Medicare enrollment during the follow-up year, had enrollment based on end stage renal disease, or were diagnosed with a non-MPN malignancy before follow-up end were excluded. Comorbidities were defined by ICD-9-CM diagnosis codes comprising the Charlson Comorbidity Index (CCI) (Charlson et al. J Chron Dis 1987;40:373–83; Deyo et al. J Clin Epidemiol 1992;45:613-9) as well as other adverse conditions. Separate non-MPN/non-cancer control groups were selected for each MPN subtype and matched (5:1) on birth year, gender, ethnicity, geography, and reason for Medicare eligibility. The proportion of patients with individual comorbidities and mean CCI during the follow-up year were compared between MPN cases and controls using univariate chi-square tests and t-tests. Results: A total of 1,355 MPN patients (n = 445 ET, 684 PV, 81 MF, 145 MPN-NOS) were identified for inclusion and assigned matching controls. For ET, PV, MF and MPN-NOS cases, respectively, mean [SD] age at index was 75.5 [9.7], 70.8 [11.3], 70.8 [10.4] and 74.1 [8.9] years and % female was 69.0, 43.9, 54.3, and 55.2. Mean [SD] years between first MPN diagnosis and study index date was 3.1 [2.0], 3.4[1.9], 2.7 [2.0], and 3.1 [2.1] for ET, PV, MF and MPN-NOS cases, respectively. Comorbidity rates during the follow-up period for MPN cases and matched controls are shown in the figure. Compared with controls, ET, PV and MPN-NOS cases had significantly (p<0.05) higher rates of serious cardiovascular events and comorbidities during the follow-up year, including myocardial infarction (ET vs. control: 8.1% vs. 4.0%, PV vs. control: 8.6% vs. 4.3%, MPN-NOS vs. control: 9.7% vs. 5.0%), congestive heart failure (CHF) (ET vs. control: 16.4% vs. 12.7%, PV vs. control: 18.4% vs. 10.1%, MPN-NOS vs. control: 22.1% vs. 12.4%), peripheral vascular disease (PVD) (ET vs. control: 20.0% vs. 15.4%, PV vs. control: 19.4% vs. 13.6%, MPN-NOS vs. control: 27.6% vs. 15.7%), and stroke (ET vs. control: 17.8% vs. 13.4%, PV vs. control: 17.8% vs. 13.1%, MPN-NOS vs. control: 22.1% vs. 13.9%). MF cases also had higher rates of CHF, PVD and stroke, but due to small sample size, only congestive heart failure was significant. Other comorbidities were significantly higher in all MPN subtypes, notably thromboembolism, renal disease, moderate-to-severe liver disease, and infections. Conclusions: Medicare enrollees with MPNs generally experienced significantly higher comorbidity rates and overall comorbidity burden (based on mean CCI scores) than matched controls. These findings have implications for both the clinical management of MPN patients as well as for health economic assessments, since a substantial portion of the cost of care for MPNs may reside in treatment of comorbidities not directly coded to MPNs. Disclosures: Davis: Eli Lilly, Merck, GlaxoSmithKline, Bristol-Myers Squibb, Pfizer, Eisai, Sanof-Aventis, Gilead Sciences, MedImmune: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Price:Eli Lilly and Company: Employment, Equity Ownership. Karve:RTI Health Solutions: Consultancy, Research Funding. Pohl:Eli Lilly and Company: Employment, Equity Ownership. Walgren:Eli Lilly and Company: Employment, Equity Ownership.

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