Epidemiologic and Clinical Characteristics of Thalassemia (Thal) Intermedia (TI) in the United States

Abstract Introduction TI is increasingly prevalent in the US due to changing immigration patterns. It is underdiagnosed, leading to inadequate or delayed management. This study reviewed the prevalence, epidemiology, and clinical characteristics of TI in patients (pts) in the US. Methods Medical records from 1/1997- 4/2014 at 4 US hematology centers were reviewed. Index date was the 1st TI visit at a center on or after 1/1/1997. Eligible pts had a TI diagnosis (≤8 mean packed red blood cell transfusions per year (yr) over a ≥3-y period after index date) and ≥12 months of follow-up. Data spanned from index date to death or last record. Descriptive analyses of demographic and clinical data were done by TI subtype. Results Of 138 pts enrolled, 84 had α-thal, 39 had β-thal, and 15 had E/β-thal. 74% of α-thal pts had deletional (del) Hb H, and 26% had non-deletional (ndel) Hb H. 59% of β-thal pts had homozygous or compound heterozygous β-globin mutations (8% with α deletion, 51% without), 20% had a single β mutation with α-gene triplication, 13% had autosomal dominant β thal, and 8% had other β-globin mutations. Of the E/β-thal pts, 80% had E/β0 and 20% had E/β+. Median age at index date was 2.3 yr (1.64 del; 6.1 ndel) in the α-thal group, 9.2 yr in the β-thal group, and 2.2 yr in the E/β-thal group. Most α-thal (77%) and E/β-thal (87%) pts were Asian; most β-thal pts were White (46%) or African-American (36%). Most α-thal (56%) and E/β-thal (53%) pts were of Southeast Asian origin; most β-thal pts were of Mediterranean (31%) or African (21%) origin. 21%, 10%, and 20% of α, β, and E/β-thal pts, respectively, were foreign-born, and 5%, 3% and 7%, respectively, were transfused outside of the US. Observation length was similar across subtypes (median: 5.3 yr). Clinical comorbidities are shown in Table 1. 22% of pts received ≥1 transfusion, while 7% of pts received ≥8 transfusions in any 1 yr to treat anemia, acute hemolysis, or cardiac abnormality; increased transfusions were initiated due to growth failure, acute hemolysis, or unspecified reasons. β-thal pts had a higher mean number of transfusions per pt per yr (PPPY) (α: 0.4 (0.0 del; 1.5 ndel), β: 0.9, E/β: 0.2) and higher mean serum ferritin (ng/mL) (204.3; 511.7; 362.4), and more often had iron chelation therapy (ICT) (11%; 28%; 7%). There was an association between higher serum ferritin, more frequent transfusions, and older age. In pts <10 yr, mean number of transfusions PPPY for regularly and ever transfused was 4.0 and 2.1, and serum ferritin for regularly, ever, and never transfused was 723.7, 438.0, and 146.4 ng/mL. In pts >18 yr, these values were 9.8 and 4.6 transfusions PPPY and 1166.8, 1042.2, and 521.4 ng/mL. An association also existed between ICT and higher mean serum ferritin (ICT: 769.9; no ICT: 463.7 ng/mL). 22% of pts had ≥1 liver iron test, and 18% had ≥1 cardiac iron test. Tested pts were older than those not tested (median yr, liver iron: 26.1 vs 7.4; cardiac: 20.1 vs 4.6). Among tested pts, 78% (25/32) had abnormal liver iron results. Median (range) LIC based on R2 or SQUID was 10.8 (2.5-18.2) mg/g dw, with corresponding within-12-month serum ferritin of 494 (127-1770) ng/mL. 49% (17/35) of pts tested had abnormal cardiac results based on electrocardiogram or echocardiogram. Table 1. Clinical comorbidities All α-thal α-thal del α-thal ndel β-thal E/β-thal N=138 N=84 N=62 N=22 N=39 N=15 Splenomegaly 54% 55% 39% 100% 51% 60% Extramedullary hematopoiesis 28% 24% 13% 55% 36% 33% Growth retardation 21% 23% 18% 36% 13% 33% Hepatomegaly 21% 24% 13% 55% 15% 20% Infections needing hospitalization/IV antibiotics 21% 25% 19% 41% 15% 13% Hypoparathyroidism/hypocalcemia 15% 17% 8% 41% 10% 20% Osteopenia/osteoporosis 13% 11% 5% 27% 21% 7% Bone deformities 9% 6% 5% 9% 21% 0% Splenectomy and/or cholecystectomy 9% 5% 2% 14% 21% 0% Cardiomegaly 4% 6% 2% 18% 0% 7% Conclusion TI in the US affects a diverse population. Our data showed a higher prevalence in African-Americans than previously documented. Rates of comorbidity and transfusion frequency increased with age. 18% and 4% of pts were born and transfused outside of the US, potentially leading to additional transfusion-related morbidity. Consistent with extant data, serum ferritin in TI often underestimated actual LIC, rendering more pts potentially eligible for ICT than observed. Morbidities observed in this study underscore the need for better and earlier diagnosis, substantiating the need for nationwide TI screening/surveillance to optimize management. Disclosures Vichinsky: Novartis: Research Funding. Kwiatkowski:Novartis: Research Funding; Sideris Pharmaceuticals: Consultancy; Shire Pharmaceuticals and Sideris Pharmaceuticals: Consultancy; ISIS: Membership on an entity's Board of Directors or advisory committees. Paley:Novartis: Employment. Vekeman:Novartis: Research Funding. Cheng:Novartis: Research Funding. Damron:Novartis: Research Funding. McCormick:Novartis: Research Funding. Sasane:Novartis: Employment. Qiu:Novartis: Employment. Duh:Novartis: Research Funding. Thompson:Bluebird bio: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Mast: Research Funding; Apopharma: Consultancy; Baxter: Consultancy, Research Funding.

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Demographic and Comorbidity Characteristics of Newly Diagnosed Multiple Myeloma Patients in the United States: A Real World Data Analysis

Blood ◽

10.1182/blood.v124.21.1301.1301 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1301-1301 ◽

Cited By ~ 3

Author(s):

Yaozhu J Chen ◽

Ajita P De ◽

Ze Cong ◽

Sanjay K Aggarwal ◽

Rolin L Wade

Keyword(s):

Real World ◽

Research Funding ◽

Index Date ◽

The United States ◽

Newly Diagnosed ◽

Real World Evidence ◽

The Us ◽

Skeletal Related Events ◽

Baseline Characteristics ◽

Baseline Demographic

Abstract Background Multiple myeloma (MM) remains an incurable plasma cell neoplasm with >20,000 new cases diagnosed annually in the United States (US). The presentation of MM is diverse and the management is guided by disease- and patient- related factors. Real world evidence regarding disease presentation is sparse for newly diagnosed MM (NDMM) patients. The goal of this study was to describe the baseline demographic and clinical characteristics of NDMM patients by linking multiple large claims databases in the US. Methods A retrospective cohort study was conducted by linking the records between 01/01/2006-12/31/2013 from three longitudinal IMS databases (Medical Claims, Pharmacy Prescriptions, and Hospital Charge Master), to reflect a complete treatment continuum for patients in all ages and by all payer types across healthcare settings. Included patients met the following criteria: ≥2 claims with a diagnosis of MM (ICD-9-CM 203.0x) at least 30 days apart between 01/01/2007-12/31/2012 (first MM diagnosis date = index date); provider stability for at least 6 months before and 3 months after index date; aged 18+ as of index date. NDMM patients were identified as those with no MM diagnosis in the 6 months pre-index. Patient baseline characteristics were assessed using data at index for age, gender, geographic region and payer type; 6-month pre-index plus index day data for Charlson Comorbidity Index (CCI); 6-month pre-index data for 32 comorbidities (e.g., cardiac arrhythmia, cerebrovascular disease, chronic kidney disease, diabetes, hypertension, among others); and 5 comorbidity categories (cardiovascular, renal, metabolic, skeletal-related events, and other). Autologous stem cell transplant (ASCT) status was also assessed based on the available follow-up data after initial diagnosis. Patient baseline characteristics were compared between the patients with versus without ASCT after MM diagnosis. Chi-square tests for categorical variables and t-tests for continuous variables (alpha=0.05) were conducted. Results The study cohort of 8,239 NDMM patients had a mean (SD) age of 66.2 (11.3) years at diagnosis, with 56.7% aged 65+; 51.8% were female; and the majority were with commercial (43.3%) or Medicare (42.8%) as payer. Patients with post-index ASCT (n=1,429; 17.3%) were distinctly different from those without (n=6,810; 82.7%): they were younger with a mean (SD) age of 58.1 (8.7) vs. 67.9 (11.1) years, fewer aged 65+, 24.1% vs. 63.5%; fewer female, 47.6% vs. 52.6% (all p<0.001); and the majority (67.5%) of patients who later had ASCT were covered by commercial plans, compared to Medicare as the biggest payer (48.2%) for those who did not have post-index ASCT. NDMM patients had an overall mean (SD) CCI score of 3.1 (1.6). Patients who later received ASCT were healthier than those who did not, with mean (SD) CCI scores of 2.7 (1.4) vs. 3.2 (1.6) (p<0.001). Close to half (47.9%) of all NDMM patients had >1 type of comorbidities at baseline. Figure 1 depicts the baseline comorbidity categories among all NDMM patients as well as the two subsets (with versus without post-index ASCT). Comorbidities were prevalent even before MM diagnosis: 43.9% of patients presented with metabolic comorbidities, 21.4% with cardiovascular diseases, 11.5% with renal conditions, 5.9% with skeletal-related events, and 45.0% with other comorbidities. The patient subset with post-index ASCT had lower comorbidity occurrences compared to those without: 10.5% vs. 23.6% in cardiovascular diseases, 5.9% vs. 12.7% in renal conditions, 32.7% vs. 46.3% in metabolic diseases (all p<0.001), consistent with literature showing that ASCT candidates tend to be younger and have less severe comorbidities. Conclusions This study provided baseline demographic and comorbidity profiles of NDMM patients and showed that the NDMM patient population presented with various comorbidities prior to the first MM diagnosis, suggesting the needs for efficacious, tolerable and safe treatment options for a heterogeneous patient population with complex disease profiles. As expected, patients who had ASCT after initial diagnosis were younger and healthier than those who did not have ASCT. The study findings portray a clearer picture of NDMM patients in the US, and provide clinicians with valuable real world evidence to identify appropriate treatment strategies for these patients. Figure 1 Figure 1. Disclosures Chen: Onyx Pharmaceuticals: Research Funding. De:Onyx Pharmaceuticals: Research Funding. Cong:Onyz Pharmaceuticals: Employment. Aggarwal:Onyx Pharmaceuticals: Employment. Wade:Onyx Pharmaceuticals: Research Funding.

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MO273A NOVEL APPROACH TO ASSESS THE DEMOGRAPHIC AND CLINICAL CHARACTERISTICS OF IMMUNOGLOBULIN A NEPHROPATHY (IGAN) PATIENTS IN A US REAL-WORLD SETTING

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab104.0031 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Raymond Przybysz ◽

Rina Mehta ◽

Gisela Rovira Tomas ◽

Carolina Aldworth ◽

Jim Doherty ◽

...

Keyword(s):

Kidney Function ◽

Clinical Characteristics ◽

Index Date ◽

Immunoglobulin A ◽

Significant Proportion ◽

Immunoglobulin A Nephropathy ◽

Targeted Interventions ◽

The Us ◽

The Mean ◽

Severe Deterioration

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is a chronic glomerular disease that affects approximately 100,000-200,000 people in the US. Approximately 15-40% of IgAN patients will eventually progress to end stage kidney disease (ESKD) within 10-20 years of diagnosis, and there is currently no targeted therapy for this disease. Decreased kidney function, persistent proteinuria and hypertension are some of the clinical manifestations of IgAN, and with demographic aspects (e.g. ethnicity) are considered as predictors of disease progression. The aim of this study is to better understand the demographic and clinical characteristics of IgAN patients in the US identified via physician notes. Method This is a descriptive, retrospective study of adult (≥ 18 years) IgAN patients in Optum® Electronic Health Records (EHRs), between January 2007 and December 2019. Optum® EHRs contain de-identified clinical and medical administrative data from 96 million people in 50 states that come from more than 140,000 providers at 740 hospitals and over 7,000 clinics. Identification of IgAN patients is challenging because there are no specific ICD codes for this disease so we used natural language processing of physician notes and chose patients with at least two IgAN records with the first one considered to be the index date, and no negative mention, as well as a biopsy procedure. Here, we present the baseline demographic and clinical characteristics of the identified patients up to 12 months before and at the index date. Results A total of 1803 patients with a biopsy record (22% of all patients with at least two IgAN records in their EHRs in our study) were included in this analysis; results are presented in Table 1. The mean age was 48 years, and the majority of patients were male (60.9%) and white (75.7%). Proteinuria levels of ≥1 g/day were found in 34% of patients. The mean eGFR was 45 ml/min/1.73m2 and 21.6% of patients had severe deterioration of kidney function (eGFR <15). The mean creatinine level was 3 mg/dL. Pain, edema and fatigue/tiredness were reported in 39.6%, 18.1% and 13.4% of patients, respectively. Hypertension was reported in 73% of patients. Based on the ICD 9 (585.6) and ICD-10 (N18.6) codes for diagnosis, 17.5% of patients had ESKD in our study. Conclusion In our cohort, a significant proportion of patients were found to have high proteinuria levels and severe deterioration of kidney function or ESKD. Moreover, edema and fatigue were recorded for a noticeable proportion of patients. In addition to the commonly reported symptoms, our study also found that pain was reported in a high proportion of patients. These findings highlight the clinical and symptom burden to patients with IgAN, suggesting that future targeted interventions are needed to reduce the burden and delay the progression of this disease.

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Abstract WP175: Stroke Prevalence Among US- and Foreign-born Adults in the United States

Stroke ◽

10.1161/str.47.suppl_1.wp175 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Jing Fang ◽

Keming Yuan ◽

Carma Ayala ◽

Renee Gindi ◽

Brian Ward

Keyword(s):

National Health Interview Survey ◽

Stroke Risk ◽

Smoking Status ◽

The United States ◽

Foreign Born ◽

Disease Mortality ◽

Stroke Prevalence ◽

The Us ◽

Interview Survey ◽

Race Ethnicity

Introduction: The proportion of US adults who are foreign-born has almost tripled since 1970. While foreign-born adults have lower cardiovascular disease mortality and risk factors (e.g., hypertension) than US-born adults, less is known about the morbidity of stroke in this population. Objective: To compare the prevalence of stroke among US adults by birthplace. Methods: We used data on 223,842 non-institutionalized adults from the 2006-2013 National Health Interview Survey. Birthplace was categorized as US- and foreign-born, and foreign-born was then grouped into 7 regions. Data on years of living in the US was included. Self-reported stroke was defined as ever being told by doctor or other health professional that s/he had a stroke. Select descriptive (age, sex, race/ethnicity, education, health insurance, language of interview, use of interpreter) and health characteristics (hypertension, diabetes, body mass index, alcohol use, smoking status) were used in analysis. Age-standardized prevalence of stroke was compared between US- and foreign-born and then by birthplace regions among foreign-born. Adjusted odd ratios (AORs) were used to assess stroke risk between US- and foreign-born after adjusting for demographic and health characteristics. Results: Sixteen percent of US adults were classified as foreign-born. Age-standardized prevalence of stroke was higher among US- than foreign-born adults overall (2.7% vs 2.0%, p<0.0001) and by race/ethnicity: non-Hispanic blacks (4.1% (US) vs 2.2% (foreign-born), p<0.0001), Hispanics (2.8% vs 2.2%, p=0.03) and non-Hispanic whites (2.5% vs 1.7%, p<0.0001). Compared to US-born men, AORs of stroke for foreign-born men by region of birth, ranged from 0.24 (95% confidence interval 0.08-0.69) for Africa to 1.05 (0.74-1.51) for Europe. Among foreign-born women, AORs ranged from 0.07 (0.01-0.43) for the Middle East to 1.13 (0.54-2.34) for Africa, after adjustment for selected characteristics. Among foreign-born adults, there was no association between age-standardized stroke prevalence and the number of years living in the US. Conclusion: Overall, foreign-born US adults had a lower prevalence of stroke than US-born adults. However, considerable heterogeneity of stroke risk was noted by region of birth.

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Does Gene Therapy in Beta Thalassemia Normalize Novel Markers of Ineffective Erythropoiesis and Iron Homeostasis?

Blood ◽

10.1182/blood-2019-129658 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 816-816 ◽

Cited By ~ 1

Author(s):

Alexis A. Thompson ◽

Tomas Ganz ◽

Mary Therese Forsyth ◽

Elizabeta Nemeth ◽

Sherif M. Badawy

Keyword(s):

Gene Therapy ◽

Stem Cell ◽

Iron Overload ◽

Serum Ferritin ◽

Research Funding ◽

Iron Homeostasis ◽

Beta Thalassemia ◽

Ineffective Erythropoiesis ◽

Liver Iron ◽

Equity Ownership

BACKGROUND: Ineffective erythropoiesis in thalassemia alters iron homeostasis, predisposing to systemic iron overload. Successful allogeneic hematopoietic stem cell transplantation (HSCT) in thalassemia major corrects anemia, should eliminate ineffective erythropoiesis (IE) and normalize iron homeostasis (IH). Whether gene therapy (GT) will fully correct IE and IH is not known. This cross-sectional observational study evaluated the iron status of patients with beta thalassemia following HSCT or GT, and compared them with cohorts of patients with thalassemia intermedia (TI) or transfusion-dependent thalassemia (TDT) using recently introduced biomarkers along with imaging studies and other clinical assessments to better understand and characterize IE and IH across groups. METHODS: We evaluated a convenience sample of 29 participants with beta thalassemia (median age 25 years, IQR 21-35; females 55%; Asian 52%). Participants in the HSCT (n=6) and GT (n=10) groups were evaluated on average 116.5 and 46.9 months following cell infusion, respectively. TDT patients (n= 9) were evaluated pre-transfusion and off iron chelation for at least 7 days, and TI (n=4) were un-transfused or not transfused in >3 years. Clinical lab assessments and MRI R2*/ T2* to assess heart and liver iron burden including post-processing, were performed using local clinical protocols. ELISAs for hepcidin, erythroferrone (Erfe) and GDF-15 were performed in a blinded manner. RESULTS: Median values for all IE and IH parameters tested were normal in the HSCT group, and were significantly lower than in all other groups. There were significant differences among all groups for hemoglobin (p=0.003), erythropoietin (Epo) (p=0.03), serum ferritin (SF) (p=0.01), transferrin (p=0.006), soluble transferrin receptor (sTfR) (p=0.02), serum hepcidin: serum ferritin (H:F) ratio (p=0.006), Erfe (p=0.001), GDF15 (p=0.003), and liver iron content (LIC) by MRI R2* (p=0.02). H:F ratio, a surrogate for predisposition to systemic iron loading, inversely correlated with Erfe (rs= -0.85, p<0.0001), GDF15 (rs= -0.69, p=0.0001) and liver R2* (rs= -0.66, p=0.0004). In a multivariate analysis, adjusted for gender and race, H:F ratio and Epo levels predicted Erfe and GDF15 (p=0.05 and p=0.06; p=0.01 and p=0.05), respectively. Even after excluding GT patients that are not transfusion independent (N=2), SF, Epo, sTfR and hepcidin remain abnormal in the GT group, and there were no significant differences in these parameters between GT and TDT. However, novel biomarkers of IH and IE suggested lower ineffective erythropoiesis in GT compared to TDT (median (IQR) Erfe, 12 (11.6-25.2) vs. 39.6 (24.5-54.7), p=0.03; GDF15, 1909.9 (1389-4431) vs. 8906 (4421-12331), p=0.02), respectively. Erfe and GDF15 were also lower in GT compared to TI, however these differences did not reach statistical significance. There were no differences in hepcidin, ferritin, or H:F by race, however Erfe and GDF15 were significantly lower in Asians compared to non-Asians (p=0.006 and p=0.02, respectively). CONCLUSION: Nearly 4 years post infusion, most subjects with TDT treated with GT are transfusion independent with near normal hemoglobin, however, studies in this limited cohort using conventional measures suggest IE and IH improve, particularly when transfusion support is no longer needed, however they remain abnormal compared to HSCT recipients, who using these parameters appear to be cured. STfR did not detect differences, however GDF15 and Erfe were more sensitive assays that could demonstrate significant improvement in IE and IH with GT compared to TDT. Contribution to IE by uncorrected stem cell populations post GT cannot be determined. Transduction enhancement and other recent improvements to GT may yield different results. Longitudinal studies are needed to determine if thalassemia patients treated with GT will have ongoing IE predisposing to systemic iron overload. Disclosures Thompson: bluebird bio, Inc.: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Baxalta: Research Funding. Ganz:Intrinsic LifeSciences: Consultancy, Equity Ownership. Nemeth:Intrinsic LifeSciences: Consultancy, Equity Ownership; Silarus Therapeutics: Consultancy, Equity Ownership; Keryx: Consultancy; Ionis Pharmaceuticals: Consultancy; La Jolla Pharma: Consultancy; Protagonist: Consultancy.

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Clinical and Economic Burden Of Peripheral T-Cell Lymphoma In The United States

Blood ◽

10.1182/blood.v122.21.2963.2963 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2963-2963

Author(s):

Michele H. Potashman ◽

Chakkarin Burudpakdee ◽

Weiying Wang ◽

Yanyan Zhu ◽

Kenneth R. Carson

Keyword(s):

Board Of Directors ◽

Economic Burden ◽

Research Funding ◽

Index Date ◽

The United States ◽

Control Group ◽

Pharmacy Services ◽

Office Visits ◽

Peripheral T Cell Lymphoma ◽

Advisory Committees

Abstract Background Peripheral T-cell lymphoma (PTCL) is an aggressive and heterogeneous subtype of non-Hodgkin lymphoma (NHL). PTCL has a poor prognosis due to advanced stage at presentation, and generally poor response to standard chemotherapy. According to recent SEER estimates, PTCL accounts for about 4% of all NHL cases in the United States each year. To date, few studies have assessed the clinical and economic burden of PTCL. Methods MarketScan data for commercially insured and Medicare supplemental patients were used to retrospectively identify unique PTCL patients. Patients were identified by ICD-9-CM diagnosis codes between October 1, 2007 and June 30, 2011. The time of first PTCL diagnosis code served as the index date, and a second PTCL diagnosis date was used for confirmation. All patients were required to have at least 6 months of continuous enrollment before and 12 months of continuous enrollment after their index date. Patients were excluded if aged <18 years, date of birth or gender were missing, or if they had received a stem cell transplant (SCT) prior to PTCL diagnosis. The control group includes patients that may have any other malignant (excluding PTCL) or non-malignant condition and are considered to represent an average insured patient population from the payer perspective. The control group was matched based on age, sex, region, plan type, payer type, and length of enrollment. Mean cost per month was measured and annualized to provide average yearly costs. Healthcare costs included hospitalizations, pharmacy services, office visits, emergency room visits, hospice stays, SCT, and other patient-related costs (lab procedures, radiology procedures, blood transfusions, and other ancillary procedures). Results Of 2820 patients with ≥1 PTCL diagnosis, 1000 patients were identified that met all inclusion criteria (mean age 56 years, 58% male), and were matched to the control group. On an average annual basis, PTCL patients were hospitalized more often (0.9 vs 0.1 hospitalizations), and experienced a longer length of stay (6.4 vs 4 days) compared with matched controls. In addition, PTCL patients had a higher utilization of office visits (16.2 vs 4.1 visits), pharmacy services (34.2 vs 11.6 prescriptions), emergency room visits (0.8 vs 0.2 visits), and hospice care (0.6 vs 0.1 stays). PTCL patients also experienced higher comorbidities (mean Charlson Comorbidity Index of 1.72 vs 0.39, as determined at index date). Overall, PTCL patients incurred much higher average annual costs compared with matched patients ($75,934.08 vs $4660.64; Table), driven mainly by hospitalizations (32.2% of overall costs) and pharmacy services (19.6% of overall costs). Conclusions PTCL is associated with high resource utilization rates and high overall costs. The development of efficacious treatments for PTCL may offer better disease management and may reduce the clinical and economic burden of PTCL. Disclosures: Potashman: Millennium: The Takeda Oncology Company: Employment. Burudpakdee:Millennium: The Takeda Oncology Company: Consulting researcher Other. Wang:Millennium: The Takeda Oncology Company: Consulting researcher Other, Research Funding. Zhu:Millennium: The Takeda Oncology Company: Employment. Carson:Millennium: The Takeda Oncology Company: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Spectrum, Inc.: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Kyowa Hakko Kirin Pharma, Inc.: Research Funding.

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Insights into Relationships Between Serum Ferritin and Liver Iron Concentration Trends during 12 Months of Iron Chelation Therapy with Deferasirox – a Post-Hoc Analysis from the Epic Study

Blood ◽

10.1182/blood.v124.21.52.52 ◽

2014 ◽

Vol 124 (21) ◽

pp. 52-52 ◽

Cited By ~ 2

Author(s):

John B Porter ◽

Mohsen Elalfy ◽

Ali T Taher ◽

Lee Lee Chan ◽

Szu-Hee Lee ◽

...

Keyword(s):

Board Of Directors ◽

Serum Ferritin ◽

Research Funding ◽

Chelation Therapy ◽

Iron Concentration ◽

Iron Intake ◽

Advisory Committees ◽

Liver Iron ◽

Baseline Serum ◽

Post Hoc

Abstract Background Serum ferritin is regularly used to assess response to chelation therapy and correlates significantly with liver iron concentration (LIC) particularly when LIC is <7 mg Fe/g dry weight (dw) and serum ferritin is <4000 ng/mL. The absence of a serum ferritin decrease in the first months of a new chelation regime may be interpreted as a lack of response with respect to decreasing body iron load. However, sequential LIC determination (where available) has indicated that many of these patients do indeed have a decrease in LIC. This clinical experience requires greater understanding, particularly the nature of the LIC and serum ferritin relationship at baseline serum ferritin values ≥4000 ng/mL. The aim of this post-hoc analysis of the EPIC study was to gain insight into the relationship between serum ferritin and LIC in response to deferasirox over 1 year, in a large patient cohort, so that serum ferritin trends can be more clearly interpreted and evidence-based practical guidance be given for patients with transfusion-dependent thalassemia (TDT). Methods TDT patients were recruited from 25 sites, received 1-year of deferasirox treatment and had serum ferritin and R2 magnetic resonance imaging (R2-MRI)-assessed LIC measurements at baseline and 1 year. Summary statistics are provided for serum ferritin and LIC responders (decrease, any change from baseline <0) and nonresponders (increase or no change, any change from baseline ≥0), and for baseline serum ferritin categories (≥4000 vs <4000 ng/mL). Results Of the 374 patients analyzed in the EPIC liver MRI substudy, 317 had TDT, of which 72.7% (n=226) had a serum ferritin response and 27.3% (n=85) had no response. Importantly, after 1 year LIC decreased in approximately half of serum ferritin nonresponders (51.8%; n=44; Table) and in 79.6% of serum ferritin responders (n=180). Median (min, Q1, Q3, max) change in LIC (mg Fe/g dw) was –5.4 (–38.5, –11.7, –0.9, 15.4) in serum ferritin responders and –0.2 (–18.4, –2.6, 2.7, 19.6) in nonresponders. Median (range) transfusional iron intake (mg/kg/day) was similar in serum ferritin responders (0.30 [0.01–1.49]) and nonresponders (0.37 [0.02–1.00]). Median deferasirox dose (mg/kg/day) was higher in serum ferritin responders than nonresponders (28.1 [9.8–40.4] vs 23.7 [9.7–37.9]). Evaluation of responses by baseline serum ferritin showed that a greater proportion of serum ferritin responders with baseline serum ferritin <4000 ng/mL also had decreased LIC (88.7% [n=102]; Table), compared with serum ferritin responders with baseline serum ferritin ≥4000 ng/mL (70.3% [n=78]). However, serum ferritin baseline category had no effect on the proportion of patients who decreased LIC despite having no serum ferritin response (52.6% [n=30], <4000 ng/mL; 50.0% [n=14], ≥4000 ng/mL; Table). There was little change in median LIC in serum ferritin nonresponders after 1 year regardless of baseline serum ferritin value (–0.3 [–13.5–18.7] for <4000 ng/mL and 0.2 [–18.4–19.6] for ≥4000 ng/mL). Assessment by change in serum ferritin and LIC quadrants indicated that patients without serum ferritin or LIC response had the lowest baseline median (range) serum ferritin and LIC (2155 [480–9725] ng/mL; 11.9 [1.8–37.5] mg Fe/g dw; n=41), and received a lower median deferasirox dose (23.7 [9.7–36.0] mg/kg/day). Overall, median LIC decrease (mg Fe/g dw) was smaller in patients with baseline serum ferritin <4000 ng/mL (n=172) than in those with serum ferritin ≥4000 ng/mL (–2.8 [–38.5–18.7] vs –4.9 [–31.1–19.6]; n=139). Median iron intake was similar between groups. Discussion and conclusions A decrease in LIC was seen in ~80% of serum ferritin responders after 1 year of deferasirox; a greater proportion of serum ferritin responders (88%) decreased LIC when baseline serum ferritin was <4000 ng/mL. Importantly, among patients with no serum ferritin response up to half may be responding with respect to iron balance, indicating that a lack of serum ferritin response should be interpreted with caution. However, since a decrease in serum ferritin predicts a decrease in LIC in 80% of patients, MRI measurement (where available) should be prioritized for patients with serum ferritin increase/no change. Overall, serum ferritin response can help predict LIC response, but in some patients treated with deferasirox, serum ferritin may not accurately reflect removal of iron from the body. Figure 1 Figure 1. Disclosures Porter: Novartis: Consultancy, Honoraria, Research Funding; Shire: Consultancy, Honoraria; Celgene: Consultancy; Cerus: Membership on an entity's Board of Directors or advisory committees; Alnylam: Membership on an entity's Board of Directors or advisory committees. Taher:Novartis: Honoraria, Research Funding. Sutcharitchan:Novartis: Research Funding. Aydinok:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Chakravarty:Novartis: Employment. El-Ali:Novartis: Employment.

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Nativity Status and Poly Tobacco Use among Young Adults in the United States

10.20944/preprints202112.0470.v1 ◽

2021 ◽

Author(s):

Peace C. Okpala ◽

Carrie Rosario ◽

Melissa J. Dupont-Reyes ◽

Michelle Y. Martin Romero ◽

Md Towfiqul Alam ◽

...

Keyword(s):

United States ◽

Young Adults ◽

Tobacco Use ◽

Regression Models ◽

The United States ◽

Foreign Born ◽

Tobacco Products ◽

Targeted Interventions ◽

Nativity Status ◽

The Us

Introduction: Young adults are the second largest segment of the immigrant population in the United States (US). Given recent trends in later age of initiation of tobacco use, we examined variation in use of tobacco products by nativity status for this population group. Methods: Our study included young adults 18-30 years of age sampled in the National Health Interview Survey (2015-2019), a nationally representative sample of the US population. We calculated prevalence of use of any and 2 or more tobacco products (cigarettes, cigars, pipes, e-cigarettes, and smokeless tobacco) for foreign-born (n=3,096) and US-born (n=6,811) young adults. Logistic regression models adjusted for age, sex, race-ethnicity, education, and poverty, while accounting for the complex survey design. Results: Foreign-born young adults were significantly less likely to use any tobacco product (Cigarette = 7.3% vs 10.7%; Cigar= 1.8% vs 4.8%; E-cigarette= 2.3% vs 4.5%, respectively; p<0.01) or poly tobacco use (1.9% vs. 4.2%; p<0.01) than US-born young adults. Adjusted regression models showed lower odds of poly tobacco use among the foreign-born than their US-born counterparts (Odds Ratio = 0.41, (95% Confidence Interval: 0.26-0.63)). Conclusion: Findings highlight the importance of targeted interventions by nativity status and further tobacco prevention efforts needed for the US-born.

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The Association Between Iron Over Load and Tanner Stage Retardation in the Females with B-Thalassemia Major

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i1.1856 ◽

2020 ◽

Vol 11 (1) ◽

pp. 546-552

Author(s):

Suzan Sabbar Mutlag

Keyword(s):

Serum Ferritin ◽

Iron Concentration ◽

Growth Failure ◽

Iron Chelation ◽

Tanner Stage ◽

Thalassemia Major ◽

The Body ◽

Liver Iron ◽

Iron Stores ◽

Female Patients

Despite optimal therapy of patients with B- major thalassemia included repeated transfusion of blood program and iron chelation agents helped by increasing survival of these patients but remained a major problem in adolescents of these patients such as growth failure and hypogonadism. This study was aimed to determine the relationship between iron overload and tanner stage retardation among female patients with B- major thalassemia in Thalassemia Hospital in Diwaniyah Governorate. The current study occurred on all female patients diagnosed β-thalassemia major depends on the blood tests, with their age range from 13years to 16 years who registered in Thalassemia unit in Al- Diwaniyah Governorate, Republic of Iraq. In the physical examination, the patients were assessed for weight, height, Tanner stages, and body mass index(BMI), which recorded. S. Ferritin value was used to assess the iron load, and pelvic ultrasound was checked to assess the size of the uterus and both ovaries. The results of the currents study revealed that the total numbers of B- thalassemia major female patients are 31 patients, aged 13-16 years. Age of patients at which diagnosed of B- major thalassemia range from 0.17 to 5 year. The frequency of Blood transfusion (time/Year) ranges from 6 to 33 times/Year. The level of serum ferritin of the patients was ranged from 913-12000 ng/ml with. Tanner stage I was predominant, accounting for 87%, whereas stage II and III accounted for 10% and 3%, respectively. There was a significant negative relation between times transfusion of blood and Tanner. There was a significant correlation between Uterus size, ovarian size, and Tanner stage. Because of inflammation falsely increase serum ferritin or due to the relation between body iron in the body and level of serum ferritin is not always within the linear range, especially in the condition of inflammation or tissue damage. So that level of serum ferritin is not an adequate measure of iron stores in patients with major thalassemia. Therefore, we needed another indicator to measure iron stores in patients with thalassemia major such as liver iron concentration.

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Disparity in Clinical Trial Opportunities for Patients with B-Cell Malignancies in the United States

Blood ◽

10.1182/blood-2018-99-117155 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4861-4861

Author(s):

Sikander Ailawadhi ◽

Sri Lekha Bodepudi ◽

Zan Tahir Shareef ◽

Fabiola Coromoto Cardozo ◽

Salman Ahmed ◽

...

Keyword(s):

United States ◽

Clinical Trial ◽

Clinical Trials ◽

Geographical Distribution ◽

Research Funding ◽

Phase 1 ◽

The United States ◽

Phase 2 ◽

B Cell Malignancies ◽

The Us

Abstract Background: Clinical trials are fundamental to advance therapeutics systematically and improve patient outcomes. Despite this, enrollment on clinical trials remains dismal in the United States (US) and is a constant focus of healthcare policy. We studied distribution of clinical trials for B-cell malignancies over time across the US and unique clinical trial opportunities i.e. individual clinical trials for the given diagnosis at a site that patients may have access to participate. Methods: We abstracted data from clinicaltrials.gov for all trials that had non-Hodgkin lymphoma (NHL) or multiple myeloma (MM) as an inclusion indication between 1999-2018. Clinical trial characteristics and distribution over US geographical divisions (West, Midwest, Northeast, and South) were studied, and differences were assessed by Chi-square test. Results: A total of 1930 trials were identified (NHL: 982, MM: 948), of which 483 were recruiting at the time of data abstraction (NHL: 250, MM: 233). Over the past 2 decades, 182691 patients were enrolled on the various trials (NHL: 81592, MM: 101099). Trials by phase of study included phase 1: 629, phase 1/2: 316, phase 2: 813, phase 2/3: 11 and phase 3: 161. Number of trials by phase separated by NHL and MM are shown in Figure 1. Of these, 197 trials were randomized (NHL: 67, MM: 130). Geographical distribution of trials by diagnosis type is shown in Figure 2. A total of 31806 unique trial opportunities were noted for MM and NHL, of which 9,513 were international and 22,293 were in the US, with a geographical distribution of 5080 in West, 8198 in Midwest, 3944 in Northeast, and 5071 in South. 4,883 of the unique trial opportunities were available at NCI/NCCN accredited sites and 17,410 were at non-NCI/NCCN sites in the US. Treatment characteristics of the trials included monoclonal antibodies in 1218, other targeted agents in 2641, stem cell transplant in 526, and other agents in 517 trials with several trials utilizing more than one of these therapeutic options. There was no statistically significant difference in the distribution of clinical trials by phase of study across various US geographical regions for MM (p=0.71), NHL (p=0.98) or combined MM+NHL (p=0.16). On the other hand, unique trial opportunities were significantly different by study phase and geographical distribution for MM, NHL or MM+NHL (all p<0.001) (Figure 3). Conclusions: Widespread access to clinical trials within a cancer diagnosis is imperative for generalizability of trial results. In a comprehensive, national analysis we noted that while it may appear that clinical trials are available across the US, sites where they are open are distributed unevenly, giving rise to a disparity in access to evidence-based therapeutic advancements for patients. Disclosures Ailawadhi: Janssen: Consultancy; Amgen: Consultancy; Pharmacyclics: Research Funding; Takeda: Consultancy; Celgene: Consultancy. Sher:Affimed: Research Funding.

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Treatment Patterns, Adverse Events, and Economic Burden in a Privately Insured Population of Newly Diagnosed Patients with Chronic Lymphocytic Leukemia in the United States

Blood ◽

10.1182/blood-2018-99-114735 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3557-3557 ◽

Cited By ~ 1

Author(s):

Shaum Kabadi ◽

Ravi K Goyal ◽

Saurabh P Nagar ◽

James A Kaye ◽

Keith L Davis ◽

...

Keyword(s):

Health Care ◽

Adverse Events ◽

Systemic Therapy ◽

Research Funding ◽

The United States ◽

Treatment Patterns ◽

Newly Diagnosed ◽

The Us ◽

Privately Insured

Abstract Introduction: Contemporary data describing treatment patterns, adverse events (AEs) and outcomes in CLL patients in clinical practice is lacking. We conducted a retrospective cohort study and assessed treatment patterns, AEs, health care resource use (HCRU), and costs in patients with newly diagnosed CLL. Methods: Using a nationally representative population of privately insured patients in the US, adult patients with CLL were selected if they had continuous health plan enrollment for ≥12 months before the first CLL diagnosis without any evidence of any CLL-directed treatment. Treatment patterns up to 4 lines of therapy (LOT) and occurrence of AEs during CLL therapies were assessed. Mean per-patient monthly HCRU and costs were assessed overall and by number of unique AEs. Results: Of all patients meeting the selection criteria (n=7,639; median age, 66 years), 18% (n=1,379) received a systemic therapy during study follow-up. The most common systemic therapy regimens, regardless of therapy line, were bendamustine/rituximab (BR) (32%), rituximab monotherapy (24% [including maintenance]), ibrutinib monotherapy (15%), and fludarabine/cyclophosphamide/ rituximab (FCR) (14%). Of these, BR was the most common LOT-1 regimen (28.1%), while ibrutinib was the most common regimen in LOT-2 (20.8%) and in LOT-3 (25.5%). Use of idelalisib was limited to 1.6% of all patients receiving systemic therapy; however, an increasing trend was observed as patients moved from first to fourth LOT (<1% in LOT-1, 3.1% in LOT-2, 4.7% in LOT-3, and 8.6% in LOT-4). AEs identified during the most common treatments for CLL are presented by treatment regimen in Table 1. The mean monthly all-cause and CLL-related costs, among patients treated with a systemic therapy, were $7,943 (SD=$15,757) and $5,185 (SD=$9,935), respectively. Figure 1 depicts mean monthly costs by care setting and number of AEs, among all patients. Mean (SD) monthly all-cause costs during the post-index date follow-up were $905 ($1,865) among those with no AEs, $1,655 ($5,364) among those with 1-2 AEs, $2,883 ($8,483) among those with 3-5 AEs, and $6,032 ($13,290) among those with ≥6 AEs. Conclusions: This population-based study yielded recent real-world evidence on treatment patterns, AEs, HCRU, and costs in patients enrolled in health plans in the US. Immunochemotherapy, particularly BR, remained the preferred frontline therapy for CLL, whereas ibrutinib was the preferred therapy in LOT-2 and LOT-3, during the study period. This study demonstrates that the AE burden associated with current treatment alternatives for CLL is substantial, and the management of AEs occurring during treatments may have a significant impact on the overall health care costs. Disclosures Kabadi: AstraZeneca: Employment. Goyal:RTI Health Solutions: Employment, Research Funding. Nagar:RTI Health Solutions: Employment, Research Funding. Kaye:RTI Health Solutions: Employment, Research Funding. Davis:RTI Health Solutions: Employment, Research Funding. Mato:Celgene: Consultancy; AstraZeneca: Consultancy; Pharmacyclics: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy; Sunesis: Honoraria, Research Funding; TG Therapeutics: Research Funding; Janssen: Consultancy, Honoraria; Acerta: Research Funding; Prime Oncology: Speakers Bureau; Regeneron: Research Funding.

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