scholarly journals Disease Characteristics of Minority Patient Populations with Polycythemia Vera: An Analysis from the Reveal Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4735-4735 ◽  
Author(s):  
Ivy Altomare ◽  
Philomena Colucci ◽  
Shreekant Parasuraman ◽  
Dilan Chamikara Paranagama ◽  
Anas Al-Janadi
Keyword(s):  
United States ◽  
High Risk ◽  
The United States ◽  
Low Risk ◽  
Employment Equity ◽  
Disease Characteristics ◽  
Reveal Study ◽  
High Risk Disease ◽  
Caucasian Patients ◽  
Equity Ownership

Abstract Introduction: Polycythemia vera (PV) is associated with increased blood cell counts, risk of thrombosis, and symptoms including fatigue and pruritus. Few studies have examined the presence or absence of racial/ethnic disparities among patients with PV. The objective of this analysis is to describe differences in disease characteristics, diagnosis, treatment, and quality of life (QOL) among Caucasian and non-Caucasian patients with PV in the United States enrolled in the prospective, observational REVEAL study. Methods: The ongoing REVEAL study (ClinicalTrials.gov ID, NCT02252159) is a prospective, multicenter, observational study of adult patients with PV in the United States. Patients were observed during a 36-month period, during which clinical data were collected from usual care visits. This analysis compared demographics, disease and clinical characteristics, disease management, comorbidities, and QOL between Caucasian and non-Caucasian patients with PV at enrollment. QOL was measured by the European Organisation for Research and Treatment of Cancer Questionnaire C30 (EORTC QLQ-C30) and Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS). Results are summarized with descriptive statistics. Results: Of the 2,510 patients enrolled in REVEAL, 2,237 were Caucasian (89.1%); 199 (7.9%) were non-Caucasian, comprised of African American (5.7%), Asian (1.5%), Native American Indian (0.2%), Pacific Islander (0.1%), and other patients (0.4%); no information was provided regarding race or ethnicity for 74 patients (2.9%). Baseline disease characteristics were similar for Caucasian and non-Caucasian groups with respect to gender and disease duration. There were no differences in method of diagnosis, laboratory values, or overall history of thrombosis between groups (Figure 1A). Mean age was higher among Caucasian patients compared to non-Caucasian patients (66.6 vs 63.8 years, respectively). The proportion of patients from rural areas was higher among Caucasian vs non-Caucasian patients (28.8% vs 12.6%); similarly, the proportion of patients from urban areas was lower among Caucasian vs non-Caucasian patients (23.1% vs 46.7%). The proportion of patients with some college or higher level of education was higher among Caucasian vs non-Caucasian patients (64.1% vs 50.3%). A higher proportion of Caucasian vs non-Caucasian patients were retired (52.0% vs 43.2%); a higher proportion of non-Caucasian patients reported being unable to work or were disabled (3.8% vs 10.1%). More Caucasian patients had high-risk disease (78.0%) compared with non-Caucasian patients (71.4%), and patients with high-risk disease were managed similarly between groups. However, Caucasian patients with low-risk disease received more phlebotomies (56.6%) than non-Caucasian patients with low-risk disease (40.4%), and over twice as many non-Caucasian patients received hydroxyurea (38.6%) than Caucasian patients (15.6%) (Figure 1B). MPN-SAF TSSs were higher for non-Caucasian patients compared with Caucasian patients, suggesting a worse symptom burden. Similarly, non-Caucasian patients reported lower functional and symptom outcomes on the EORTC QLQ-C30, including a disparity in financial difficulties, compared to Caucasian patients (Figure 1C). Conclusions: This analysis evaluated a cohort of racial/ethnic minority patients with PV treated in the United States. As in other cancer-related trials, there is a risk that racial and ethnic minorities may be underrepresented in REVEAL. With this limitation in mind, in this analysis, differences were not observed among Caucasian and non-Caucasian patients with respect to method of diagnosis, duration of disease, thrombosis rates, or management of high-risk disease. Non-Caucasian patients demonstrated higher rates of low-risk disease and cytoreductive therapy for low-risk disease yet had worse symptom burden, lower functional scores, and greater disability. This study underscores the importance of symptom assessment and ancillary resource availability for patients with PV Disclosures Altomare: Bayer: Consultancy; Genentech: Consultancy; Ipsen: Other: Advisory Board Member; Celgene: Other: Advisory Board Member; Incyte: Consultancy; Novartis: Consultancy; Amgen: Consultancy. Colucci:Incyte: Employment, Equity Ownership. Parasuraman:Incyte: Employment, Equity Ownership. Paranagama:Incyte: Employment, Equity Ownership.

scholarly journals Persistence of Ruxolitinib Treatment in Patients with Myelofibrosis at Community Oncology Practices in the United States-Contemporary Data

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5385-5385
Author(s):  
Jingbo Yu ◽  
Jonathan K. Kish ◽  
Dilan Paranagama ◽  
Philomena Colucci
Keyword(s):  
United States ◽  
High Risk ◽  
Chart Review ◽  
The United States ◽  
Current Analysis ◽  
First Line ◽  
Employment Equity ◽  
Persistence Rates ◽  
Equity Ownership

Introduction Myelofibrosis (MF) is a chronic myeloproliferative neoplasm frequently associated with debilitating disease-related symptoms and shortened overall survival (OS). Ruxolitinib, a Janus kinase (JAK)1/JAK2 inhibitor, was approved on November 16, 2011 for patients with intermediate- and high-risk MF. The phase 3 COMFORT trials demonstrated that ruxolitinib reduced spleen volume, improved MF-related symptoms, and prolonged OS. In the COMFORT trials, the median duration of ruxolitinib treatment was 2.8 years (5-year pooled analysis). The objective of this real-world chart review study is to describe persistence of ruxolitinib treatment early on in the treatment course in patients with MF at community hematology/oncology practices in the United States. Methods Medical charts from community hematology/oncology practices in Cardinal Health Oncology Provider Extended Network (OPEN) were reviewed and abstracted into electronic case report forms by physicians. Physicans were instructed to abstract data from the earliest eligible patients and then chronologically, thereafter. This analysis included adult patients diagnosed with primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF between 01/2012 and 12/2016. Patients were required to have intermediate- or high-risk MF (based on a data-derived International Prognostic Scoring System [IPSS] risk categorization), have platelet count >50 × 109/L at the time of diagnosis, have received ruxolitinib as first-line treatment, and have ≥6 months of follow up after the initiation of ruxolitinib; patients who died within 6 months of initiation of ruxolitinib were considered as discontinued patients and were included in the analysis. Three- and 6-month persistence rates are reported. Results A total of 141 patients from 22 community hematology/oncology practices were included in the analysis; 3 patients who were still on ruxolitinib at the end of the study period, but with less than 6 months of follow up, were excluded from the analysis. Mean (SD) age at diagnosis was 69.8 (10.2) years, 61.7% were male, 71.6% had primary MF, and 56.7% were high-risk at diagnosis. Median time from diagnosis to ruxolitinib initiation was 36 (interquartile range [IQR], 20-91) days. The majority of patients initiated ruxolitinib in 2016 or later (Figure). The starting dose of ruxolitinib was 5 mg twice daily [BID] in 7.8%, 10 mg BID in 9.9%, 15 mg BID in 39.7%, 20 mg BID in 34.8%, and 25 mg BID in 7.8%. Three- and 6-month persistence rates were 97.2% and 91.5%, respectively (Table). Discussion A previous retrospective chart review of prescription claims and patient level data evaluated a cohort of patients with MF prescribed ruxolitinib just prior to and shortly after its approval (November 1, 2011 to August 31, 2012); in that study, 3- and 6-month persistence rates of 39.1% and 27.0%, respectively, were reported (Blood. 2013[122]:2833). In the current study, the 3- and 6-month persistence rates were notably higher at 97.2% and 91.5%, respectively. These higher rates are likely attributable to a number of factors. The current analysis was limited to patients treated first-line with ruxolitinib. Furthermore, the index period in the current analysis extended almost 5 years beyond ruxolitinib approval; in this 5-year period, there were a number of publications in support of ruxolitinib dose optimization with particular focus on the first 8-12 weeks of treatment (J Hematol Oncol. 2013[6]:79; Int J Hematol. 2016[104]4:420-9). The 3- and 6-month persistence rates reported here demonstrate that only a small proportion of patients with myelofibrosis treated with first-line ruxolitinib discontinued the drug early on in their treatment course. Conclusion This contemporary analysis demonstrates high rates of 3- and 6-month persistence of first-line ruxolitinib in patients with MF treated in community practices. Proper monitoring and management of the expected mechanism-based toxicity of a JAK inhibitor and proper dose titration for insufficient response, early in the treatment course, may help patients derive maximum, long-term benefits from ruxolitinib. Disclosures Yu: Incyte: Employment, Equity Ownership. Kish:Cardinal Health: Employment. Paranagama:Incyte: Employment, Equity Ownership. Colucci:Incyte: Employment, Equity Ownership.

scholarly journals A Novel Prognostic Model That Is Superior to FLIPI-1 and FLIPI-2 and Integrates Clinical and Treatment Factors to Predict Progression-Free Survival and Early Treatment Failure in Patients with Follicular Lymphoma in the GALLIUM Trial

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2872-2872 ◽  
Author(s):  
Farheen Mir ◽  
Andrew Grigg ◽  
Michael Herold ◽  
Wolfgang Hiddemann ◽  
Robert Marcus ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Research Funding ◽  
Prognostic Model ◽  
Low Risk ◽  
Prognostic Variables ◽  
Advisory Committees ◽  
High Risk Disease ◽  
Risk Patients ◽  
Equity Ownership

Abstract Introduction: Progression of disease within 24 months of initial therapy (POD24) is associated with poor survival in patients with follicular lymphoma (FL). Existing prognostic models, such as FLIPI-1 and FLIPI-2, show poor sensitivity for POD24, and are derived from cohorts lacking bendamustine-treated patients. More accurate predictive models based on current standard therapies are needed to identify patients with high-risk disease. The Phase III GALLIUM trial (NCT01332968) compared the safety and efficacy of standard chemotherapy regimens plus rituximab (R) or obinutuzumab (G) in patients with previously untreated FL. Using GALLIUM data, we developed a novel risk stratification model to predict both PFS and POD24 in FL patients after first-line immunochemotherapy. Methods: Enrolled patients were aged ≥18 years with previously untreated FL (grades 1-3a), Stage III/IV disease (or Stage II with bulk), and ECOG PS ≤2, and required treatment by GELF criteria. Patients were randomized to receive either G- or R-based immunochemotherapy, followed by maintenance with the same antibody in responders. The chemotherapy arm (CHOP, CVP, or bendamustine) was selected by each study center. POD24 was defined as progressive disease or death due to disease within 24 months of randomization (noPOD24 = no progression or lymphoma-related death in that period). The most strongly prognostic variables, based on PFS hazard ratios, were estimated using penalized multivariate Cox regression methodology via an Elastic Net model. Selected variables were given equal weights, and a clinical score was formed by summating the number of risk factors for each patient. Low- and high-risk categories were determined using a cut-off that provided the best balance between true- and false-positives for PFS. PFS correlation and sensitivity to predict POD24 were assessed. The data used are from an updated GALLIUM efficacy analysis (data cut-off: April 2018; median follow-up: 57 months). Results: 1202 FL patients were enrolled. Based on data availability and biological plausibility (i.e. could reasonably be linked with high-risk disease), 25 potential clinical and treatment-related prognostic variables were entered into the Elastic Net model (Table). A model containing 11 factors was retained by the methodology and chosen as the best model (Table). Patients were categorized as 'low risk' if they scored between 0 and 3 (n=521/1000 patients with complete data) and as 'high risk' if they scored between 4 and 11 (n=479/1000 patients). At 2 years, the PFS rate was 84.5% in the whole FL population. Using our model, 2-year PFS for high-risk patients was 77% compared with 79.9% for FLIPI-1 and FLIPI-2. In low-risk patients, 2-year PFS was 92% compared with 87.9% for FLIPI-1 and 87.6% for FLIPI-2 (low-intermediate-risk patients). Our model increased the inter-group difference in 2-year PFS rate from 8% (FLIPI-1) and 7.7% (FLIPI-2) to 15%. At 3 years, the inter-group difference increased from 6.9% (FLIPI-1) and 9% (FLIPI-2) to 17% (Figure). Sensitivity for a high-risk score to predict POD24 was 73% using our model compared with 55% for FLIPI-1 and 52% for FLIPI-2 (based on 127 POD24 and 873 noPOD24 patients with complete data). Excluding patients who received CVP, which is now rarely used, resulted in an inter-group difference in PFS of 15% at 2 years and 16.8% at 3 years. A sensitivity analysis showed that inclusion of the 9 clinical factors only (i.e. removal of CVP and R treatment as variables) formed a more basic scoring system (low-risk patients, 1-3; high-risk patients, 4-9); the inter-group difference in PFS was 16.5% at 2 years and 17.6% at 3 years. However, sensitivity for POD24 decreased to 56%. Conclusion: Our clinical prognostic model was more accurate at discriminating patients likely to have poor PFS than either FLIPI-1 or FLIPI-2, and its prognostic value was sustained over time. Our model also identified the FL population at risk of POD24 with greater sensitivity. Variables such as age and bone marrow involvement were not retained by our model, and thus may not have a major impact in the current era of therapy. Factors such as sum of the products of lesion diameters were included, as this captures tumor burden more accurately than presence of bulk disease. Future studies will aim to improve the accuracy of the model by considering gene expression-based prognostic markers and DNA sequencing to form a combined clinico-genomic model. Disclosures Mir: F. Hoffmann-La Roche: Employment. Hiddemann:F. Hoffman-La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Consultancy, Research Funding. Marcus:F. Hoffman-La Roche: Other: Travel support and lecture fees; Roche: Consultancy, Other: Travel support and lecture fees ; Gilead: Consultancy. Seymour:Genentech Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Consultancy; AbbVie: Consultancy, Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Bolen:Roche: Other: Ownership interests PLC*. Knapp:Roche: Employment. Launonen:Launonen: Other: Ownership interests none PLC; Travel, accommodation, expenses; Novartis: Consultancy, Equity Ownership, Other: Ownership interests none PLC; Travel. accommodation, expenses; Roche: Employment, Other: Travel, accommodation, expenses. Mattiello:Roche: Employment. Nielsen:F. Hoffmann-La Roche Ltd: Employment, Other: Ownership interests PLC. Oestergaard:Roche: Employment, Other: Ownership interests PLC. Wenger:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership, Other: Ownership interests PLC. Casulo:Gilead: Honoraria; Celgene: Research Funding.

scholarly journals Impact of Myeloproliferative Neoplasms on Patients' Employment and Income: Findings from the Living with MPN Survey

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2250-2250
Author(s):  
Simon Condliffe ◽  
Jingbo Yu ◽  
Dilan Chamikara Paranagama ◽  
Shreekant Parasuraman
Keyword(s):  
United States ◽  
Employment Status ◽  
Early Retirement ◽  
Myeloproliferative Neoplasms ◽  
Good Health ◽  
The United States ◽  
Employment Equity ◽  
Disability Leave ◽  
Part Time ◽  
Equity Ownership

Abstract Background: Patients with myeloproliferative neoplasms (MPNs), including myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET), experience a high symptom burden that may compromise daily functioning and quality of life. The objective of this analysis was to evaluate income loss associated with disease-related employment changes among patients with MPNs in the United States. Methods: The Living with MPN survey was completed online by adult patients (aged 18-70 years) with MF, PV, or ET in the United States between April and November of 2016. Respondents employed at the time of MPN diagnosis were asked questions about disease-related changes in employment status and salaries occurring between diagnosis and the year of survey (2016). In addition, details related to patient demographics, MPN diagnosis, and MPN-related symptoms were collected. Cumulative income losses as a result of disease-related employment changes up to the time of the survey were calculated based on the timing of employment changes and salaries, which were reported in nominal dollars. Results: Of the 904 survey respondents, 592 (65%) were employed at the time of MPN diagnosis. Among those employed, mean age was 54.0 years, 70.6% were female, and 72.3% were married or had domestic partners at the time of survey. The average duration of disease was 6.1 years (MF, 4.6; PV, 6.9; ET, 6.3). Approximately half (50.5%) of the employed respondents experienced at least one change in employment status because of their diagnosis. Employment status changes and associated impact on income in patients with MPNs was greatest for those who took early retirement, medical disability leave, or left a job due to their disease ($419,610, $169,048, $168,245, respectively). Respondents who changed from full- to part-time employment, reduced hours, or were reassigned to a lower-paying job because of their disease also reported income losses ($79,492, $47,104, $51,872, respectively; Table). Among respondents who were 45-64 years old at the time of the survey (n=383), 18.8% reported retiring early as a result of their disease. In comparison, according to nationally representative data from the Medical Expenditures Panel Survey (MEPS), only 7.8% of individuals aged 45-64 years in excellent or very good health and 9.2% of individuals in poor health reported being retired (longitudinal data set 2014-2015). Moreover, 30.5% (117/383) of respondents aged 45-64 years in the Living with MPN survey reported leaving a job as a result of their disease. In comparison, 5.5% of MEPS individuals aged 45-64 years in excellent or very good health and 16.4% of individuals in poor health were working at the start of 2014 but not by the end of 2015. Conclusions: About half of employed patients living with MPNs experienced a variety of employment changes as a result of their disease, which in turn had a considerable impact on income. The most frequently reported disease-related employment change was leaving a job, followed by medical disability leave, reduced hours, early retirement, switching from full-time to part-time, and being reassigned to a lower-paying job. Patients 45-64 years old with MPNs were more than twice as likely to have left a job or retired early compared with an age-matched US general population cohort. On average, the foregone income due to disease-related employment changes was greatest for early retirees ($419,610), followed by those who went on medical disability leave ($169,048), and left a job ($168,245). Early, effective management of MPNs and associated symptoms may help patients avoid these disease-related changes to their employment status and the subsequent economic and financial impact. Disclosures Condliffe: Incyte Corporation: Consultancy. Yu:Incyte Corporation: Employment, Equity Ownership. Paranagama:Incyte: Employment, Equity Ownership. Parasuraman:Incyte: Employment, Equity Ownership.

Registry Of Patients Treated With Protein C Concentrate (Human) In The United States and Europe: Interim Results

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1146-1146
Author(s):  
Marilyn J. Manco-Johnson ◽  
Paul Knoebl ◽  
Amy D. Shapiro ◽  
Maureen Finnerty ◽  
Leman Yel ◽  
...  
Keyword(s):  
United States ◽  
Board Of Directors ◽  
Research Funding ◽  
Protein C ◽  
The United States ◽  
Employment Equity ◽  
Advisory Committees ◽  
Protein C Concentrate ◽  
Concentrate Treatment ◽  
Equity Ownership

Abstract Background Protein C (PC) is a naturally occurring, vitamin-K dependent anticoagulant produced by the liver. Deficiency of PC, which can be congenital or acquired, results in a hypercoagulable state. Patients with severe PC deficiency may manifest severe, often life-threatening, disseminated intravascular coagulation (DIC), purpura fulminans (PF), and/or thromboembolism. Highly purified protein C concentrate prepared from human donor plasma (Ceprotin; Baxter Healthcare Corporation, Westlake Village, CA) is an approved therapy for prevention and treatment of venous thrombosis and PF in patients with severe congenital PC deficiency (SCPCD) in the United States. It is indicated in patients with SCPCD for PF and coumarin-induced skin necrosis, and short-term prophylaxis in the European Union and other countries. Use of protein C concentrate (human) has been reported in patients with acquired PC deficiency. The Ceprotin Treatment Registry is a prospective, international, multi-center, open-label, non-interventional, observational study designed to examine the long-term safety and effectiveness of protein C concentrate (human) in the clinical setting. This is the first large, real-world assessment of the treatment of a rare disease with protein C concentrate (human). Here we report data from the first interim analysis in June 2013 covering a 3-year enrollment period. Methods Patients of any age who received, or were initiating/receiving protein C concentrate are included. The study duration is 5 years (3-year enrollment period plus 2 years of follow-up). All study visits/assessments are in accordance with standard of care, with protein C concentrate dose, dose frequency, duration and route of administration determined by the investigator. The study objectives are to determine the most common medical diagnoses associated with protein C concentrate treatment, protein C concentrate treatment regimens, and safety information based on all serious adverse events (SAEs) and rate of treatment-related AE. Other objectives include: an examination of the relationship between protein C concentrate treatment and outcomes in all registry participants, as well as various subgroups. Descriptive statistical analyses are used. Results At the time of data extraction, 34 patients were enrolled from 26 centers; 10 centers in the United States and 16 centers in Europe. Half of the patients were males. The primary diagnosis of PC deficiency was congenital in 25 patients (73.5%) and acquired in 9 patients (26.5%). The median age at diagnosis was 0.03 years (range 0–19.9). Mean plasma PC activity level was 9% (range 1–40.0). The most common (in ≥3 patients) thrombotic disease-associated conditions were PF (50.0%); blindness (44.1%); thromboembolic disease (41.2%), which included deep vein thrombosis, arterial thrombosis and DIC; stroke (32.4%), and renal dysfunction (8.8%). Of the 23 patients being treated with protein C concentrate, 15 were administered protein C concentrate intravenously, and 8 patients received protein C concentrate subcutaneously. The body weights of patients receiving subcutaneous treatment ranged from 10.0 kg to 57.9 kg. A total of 15 patients received an anticoagulant treatment in addition to protein C concentrate. Eight patients reported 23 SAEs, all of which were considered not related to treatment. Eighteen (52.9%) patients reported 72 AEs; only 1 of them, an episode of upper respiratory infection, was considered possibly treatment-related. In 18 patients in whom PC activity recovery was determined after protein C concentrate treatment, there were no patients documented with poor recovery. Protein C concentrate was used during 18 surgeries/invasive procedures and considered effective in all interventions for which data were available. Conclusions Data from the first interim analysis of the Ceprotin Treatment Registry demonstrate that patients with both congenital and acquired severe PC deficiency who are treated with protein C concentrate (human) have a low incidence of treatment related SAEs and AEs, and treatment with protein C concentrate appears to be effective when used during surgery/invasive procedures. Further patient follow up will shed light onto clinical treatment outcomes. Disclosures: Manco-Johnson: CSL Behring: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Novo Nordisk: Membership on an entity’s Board of Directors or advisory committees; Biogen Idec: Membership on an entity’s Board of Directors or advisory committees; Baxter BioScience: Membership on an entity’s Board of Directors or advisory committees; Bayer HealthCare: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Eisai: Research Funding. Knoebl:Novo Nordisk: Consultancy, Honoraria; Baxter: Consultancy, Honoraria. Shapiro:Cangene: Research Funding; Biogen Idec: Research Funding; Baxter BioScience: Research Funding; Bayer HealthCare: Research Funding. Finnerty:Baxter: Employment, Equity Ownership. Yel:Baxter: Employment, Equity Ownership. Gelmont:Baxter: Employment, Equity Ownership.

Defibrotide for the Treatment of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome Following Hematopoietic Stem Cell Transplantation or Chemotherapy--Results from the Italian Therapeutic Use Protocol

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3107-3107 ◽  
Author(s):  
Franco Locatelli ◽  
Maura Faraci ◽  
Simone Cesaro ◽  
Daria Pagliara ◽  
Franca Fagioli ◽  
...  
Keyword(s):  
United States ◽  
Distress Syndrome ◽  
Treatment Protocol ◽  
The United States ◽  
Therapeutic Use ◽  
Occlusive Disease ◽  
Sinusoidal Obstruction Syndrome ◽  
Employment Equity ◽  
Hematopoietic Stem ◽  
Equity Ownership

Introduction Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is an unpredictable, potentially life-threatening complication of chemotherapy (CT) given as conditioning for hematopoietic stem cell transplantation (HSCT), or as primary treatment. Severe hepatic VOD/SOS, traditionally defined by occurrence of multi-organ dysfunction/failure (MOD/MOF), may be associated with mortality rates >80%. In the European Union, defibrotide is approved for treatment of severe VOD/SOS post-HSCT. It is not approved in the United States, but is available through an expanded-access program. Here, we report the results of an Italian therapeutic use program, defibrotide treatment protocol (TUT), in which defibrotide was provided upon physician request for treatment of patients with VOD/SOS. Methods This was a multicenter, single-arm, open-label program of defibrotide treatment in patients with hepatic VOD/SOS, with or without MOD/MOF, from 2010-2014. Patients were eligible if they were diagnosed with VOD/SOS having met ≥2 of the following criteria: bilirubin (>2 mg/dL), ascites, unexplained weight gain >5% above baseline (weight on day 1 of HSCT conditioning or CT), or hepatomegaly. Patients with biopsy-proven VOD/SOS were also eligible. Exclusion criteria were use of anticoagulants (beyond those for IV line maintenance), significant uncontrolled acute bleeding (transfusions after dialysis were allowed), pregnancy, and hemodynamic instability requiring >2 vasopressor drugs. MOD/MOF was defined as renal (creatinine >3x baseline, creatinine clearance or glomerular filtration rate <40% of baseline, or dialysis dependence) or pulmonary (oxygen saturation <90% on room air, requiring oxygen supplementation, or ventilator dependence) dysfunction. Patients were treated with defibrotide 25 mg/kg/d in 4 divided doses given intravenously over 2 hours each. Outcomes included survival at day +100 post-HSCT or post-CT and adverse events (AEs). VOD/SOS and MOD/MOF were not reported as AEs unless the event was considered serious. Demographics and AEs were analyzed using descriptive statistics; efficacy was estimated by the SAS/STAT LifeTest Procedure. Results A total of 98 patients had hepatic VOD/SOS (92% had VOD/SOS post-HSCT [81% allogeneic, 10% autologous, 1% unknown], 8% post-CT); of these, 21% had MOD/MOF and 79% did not. Median age was 13.4 years (range 0-68; 57 [58%] aged <18 years and 41 [42%] ≥18 years), 55% were male, and 65% were white. The most common primary diseases were acute myelogenous leukemia (25%) and acute lymphoblastic leukemia (19%). The most common prophylaxis regimens for graft-vs-host disease (GvHD) were reported as cyclosporine + methotrexate (38%), cyclosporine (12%), and cyclosporine + methotrexate + other (12%); tacrolimus- and sirolimus-containing regimens, which have been associated with development of VOD/SOS, were received by 5% and 4% of patients, respectively. The median defibrotide dose was 25 mg/kg/d (range, 6.15-40.0) and median duration of treatment was 14 days (range: 1-84). The estimated day +100 survival for all patients was 68.4% (95% CI, 58.0%-76.7%). Day +100 survival in post-HSCT patients was 67.0% (95% CI, 56.2%-75.8%) and for post-CT patients was 85.7% (95% CI, 33.4%-97.9%). Across the entire study, 38 deaths were reported; primary causes were progression of VOD/SOS and MOD/MOF (44.7%), infection (21.1%), GvHD (15.8%), and disease progression (13.2%). Treatment-emergent AEs were reported in 21% of patients in this therapeutic use program; the most common (reported in ≥2 patients) were MOD/MOF (9%), VOD/SOS (6%), and cytomegalovirus infection and acute respiratory distress syndrome (2% each). Treatment-related AEs were reported by 5% of patients, and included hemorrhagic cystitis, urinary tract hemorrhage, hemorrhages (unspecified), hemorrhagic diathesis, and pulmonary hemorrhage (1 patient each). Serious AEs were reported in 15% of patients, most commonly MOD/MOF (7%), VOD/SOS (4%), and acute respiratory distress syndrome (2%). Conclusion In the Italian therapeutic use program, defibrotide treatment protocol (TUT), approximately one-fifth of the patients with hepatic VOD/SOS had MOD/MOF. The estimated survival rate of 68.4% at day +100, and the AE profile, was consistent with efficacy and safety data reported in previous studies in similar VOD/SOS patient populations. Support: Jazz Pharmaceuticals. Disclosures Off Label Use: Defibrotide is an investigational treatment for hepatic veno-occlusive disease/sinusoidal obstruction syndrome in the United States.. Amber:Jazz Pharmaceuticals: Employment, Equity Ownership. Banerjee:Jazz Pharmaceuticals: Employment, Equity Ownership. Finetto:Gentium S.p.A.: Employment; Jazz Pharmaceuticals: Equity Ownership.

Prostate cancer in the British Asian population: A case-control study

2020 ◽  
pp. 205141582096957
Author(s):  
Luke R Forster ◽  
Clare Jelley ◽  
Charles E Breeze ◽  
Rajindra Singh ◽  
Rohit Chahal ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Active Surveillance ◽  
Asian Population ◽  
Short Term ◽  
Disease Characteristics ◽  
Co Morbidity ◽  
High Risk Disease ◽  
Caucasian Patients ◽  
Control Study

Objectives: To study demographic and disease variables at presentation, diagnosis and treatment of prostate cancer in British South Asian (SA) men and compare with their Caucasian counterparts. Methods: A retrospective review of prostate cancer cases between 2010 and 2015 identified patients of SA descent who were matched for age, residential location and year of diagnosis with two Caucasian patients. Disease characteristics, treatment and short-term outcomes were recorded and compared. Results: A total of 1274 patients were diagnosed, of which 50 (3.9%) were SA. SA patients had less screen-detected prostate cancer (12% versus 31%, p=0.02), more co-morbidity and more high-risk disease (57% versus 37%, p=0.03). Active surveillance was the preferred treatment option (32%) with 2% having surgery compared with 22% ( p=0.003) from the Caucasian cohort. Logistic regression showed these disparities to be related to the different presentations. Conclusion: SA men with prostate cancer are less likely to be diagnosed following asymptomatic screening and the majority have high-risk disease at presentation. These differences lead to SA men preferring active surveillance to radical surgery. Given the increasing British Asian population, the findings demonstrate a need for research and public health interventions to better understand and address the differences noted between these groups.

scholarly journals Relationship Between Lenalidomide Dose Modification and Outcomes in Patients with Myelodysplastic Syndromes

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3286-3286
Author(s):  
Amy E. DeZern ◽  
Gary Binder ◽  
Albert Fliss ◽  
X. Henry Hu ◽  
Syed Rizvi ◽  
...  
Keyword(s):  
High Risk ◽  
Myelodysplastic Syndromes ◽  
Real World ◽  
Employment Equity ◽  
Dose Modification ◽  
Real World Setting ◽  
Improved Outcomes ◽  
High Risk Disease ◽  
Equity Ownership ◽  
Dose Modifications

Abstract Introduction: In clinical studies of patients (pts) with International Prognostic Scoring System (IPSS)-defined Low- to Intermediate-1-risk myelodysplastic syndromes (MDS), dose modification of lenalidomide (LEN) has been commonly used by physicians to sustain control of disease while managing toxicities. A previous real-world setting analysis has shown that dose modification of LEN in pts with multiple myeloma was associated with longer duration of therapy (DOT) and improved outcomes versus pts without dose modification (Usmani SZ, et al. Blood. 2014;124:abstract 2655). This study aimed to evaluate whether LEN dose modification in pts with MDS is associated with longer DOT and improved outcomes in a real-world setting using various measures available from claims data. Methods: A retrospective study was conducted using a large US medical and pharmacy claims database, covering > 25 million commercial- and Medicare-insured lives annually. MDS pts with ≥ 2 outpatient claims or ≥ 1 inpatient medical claim associated with a diagnosis of MDS (ICD-9-CM codes 238.72-238.75) were identified; the first such claim was defined as the index date. A minimum of 12 months' pre-index enrollment and 6 months' post-index continuous enrollment between Jan 1, 2008 and Dec 31, 2013 was required. The inclusion criteria included pts with MDS treated with LEN who did not have claims for stem cell transplantation or high-risk disease at diagnosis. Clinically relevant metrics, including DOT, time to acute myeloid leukemia (AML), time to next therapy, time to advancement to high-risk disease (as measured by ICD-9-CM code 238.73), and time to red blood cell transfusion dependence, were compared in pts with and without LEN dose modifications (defined as: change in dose [mg/day], dose interruption of 10-60 days, or both); time-to-progression (TTP) was defined as a composite of the above. Charlson Comorbidity Index (CCI) and MDS Comorbidity Index (MDS-CI) (Della Porta MG, et al. Haematologica. 2011;96:441-9) scores were determined to compare baseline measures between groups. Adjusted hazard ratios (HRs) were calculated using a Cox proportional hazards model adjusted for age group, sex, and MDS-CI risk group at LEN initiation. Results: Of 529 pts who met inclusion criteria, 245 (46%) had LEN dose modifications, including 135 pts with ≥ 1 dose change and 201 pts with ≥ 1 dose interruption; 91 pts had both. Overall, 54% of pts were aged ≥ 75 years; age (P = 0.647), CCI (P = 0.867), and MDS-CI (P = 0.967) did not differ between pts managed with and without LEN dose modifications. For pts without dose modifications, the rate of cytopenias within 14 days prior to discontinuation (50.7%) did not significantly differ from the rate of cytopenias within 14 days prior to first modification for pts with dose modifications (50.2%; P = 0.920). Median time to first dose modification was 1.9 months (range 0.4-23.2). Median DOT was 12.6 months for pts with LEN dose modification versus 1.9 months for pts without dose modification (P < 0.0001). The DOT benefit did not differ whether the modification was a dose change or an interruption (P = 0.115). Most pts initiated LEN at a 10 mg/day dose; the most common change for those who modified was to reduce to a 5 mg/day dose. Median TTP was 20.6 months for pts with dose modification versus 13.7 months for those without; the adjusted HR was 0.703 (95% confidence interval 0.541-0.914) (P = 0.009). Pts with dose modification had statistically significant improvements in time to AML (P = 0.018), time to next therapy (P = 0.002), and time to high-risk disease (P = 0.043) compared with pts without dose modification. Conclusions: For pts medically managed with lenalidomide treatment for myelodysplastic syndromes in the USA, dose modifications during their treatment were associated with longer therapy duration, improvement in time to progression to AML or high-risk disease, and improved time to next therapy compared with pts without lenalidomide dose modification. Modifications were utilized in 46% of pts and the median time to modifications was similar to the DOT in those not receiving modifications, suggesting dose modifications may be worth considering for some pts who discontinue lenalidomide. This analysis supports lenalidomide dose modification in the treatment of MDS as an effective technique in the real-world setting for pts to achieve better treatment outcomes based on proxy measures available from claims data. Disclosures Binder: Celgene Corporation: Employment, Equity Ownership. Fliss:Celgene Corporation: Employment, Equity Ownership. Hu:Celgene Corporation: Employment, Equity Ownership, Patents & Royalties. Rizvi:Celgene Corporation: Employment, Equity Ownership. Corvino:Genesis Research LLC: Consultancy. Arikian:Genesis Research LLC: Consultancy. Surinach:Genesis Research LLC: Consultancy. Lee:Genesis Research LLC: Consultancy.

scholarly journals Potential Contributions of Clinical and Community Testing in Identifying Persons with Undiagnosed HIV Infection in the United States

2020 ◽  
Vol 19 ◽  
pp. 232595822095090
Author(s):  
James G. Kahn ◽  
Eran Bendavid ◽  
Patricia M. Dietz ◽  
Angela Hutchinson ◽  
Hacsi Horvath ◽  
...  
Keyword(s):  
United States ◽  
High Risk ◽  
Hiv Infection ◽  
Hiv Testing ◽  
Clinical Care ◽  
The United States ◽  
Low Risk ◽  
Published Data ◽  
Community Settings ◽  
Undiagnosed Hiv

Background: An estimated 166,155 individuals in the United States have undiagnosed HIV infection. We modeled the numbers of HIV-infected individuals who could be diagnosed in clinical and community settings by broadly implementing HIV screening guidelines. Setting: United States. Methods: We modeled testing for general population (once lifetime) and high-risk populations (annual): men who have sex with men, people who inject drugs, and high-risk heterosexuals. We used published data on HIV infections, HIV testing, engagement in clinical care, and risk status disclosure. Results: In clinical settings, about 76 million never-tested low-risk and 2.6 million high-risk individuals would be tested, yielding 36,000 and 55,000 HIV diagnoses, respectively. In community settings, 30 million low-risk and 4.4 million high-risk individuals would be tested, yielding 75,000 HIV diagnoses. Conclusion: HIV testing in clinical and community settings diagnoses similar numbers of individuals. Lifetime and risk-based testing are both needed to substantially reduce undiagnosed HIV.

scholarly journals Disease and Clinical Characteristics of Patients with Myelofibrosis Enrolled in the MOST Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4190-4190
Author(s):  
Aaron T. Gerds ◽  
Roger M. Lyons ◽  
Philomena Colucci ◽  
Patricia Kalafut ◽  
Dilan Paranagama ◽  
...  
Keyword(s):  
Research Funding ◽  
Clinical Characteristics ◽  
The United States ◽  
Treatment Patterns ◽  
Low Risk ◽  
Normal Range ◽  
Employment Equity ◽  
Oncology Research ◽  
Risk Patients ◽  
Equity Ownership

Introduction: Myelofibrosis (MF) is a chronic Philadelphia chromosome-negative myeloproliferative neoplasm characterized by progressive bone marrow (BM) fibrosis, extramedullary hematopoiesis, splenomegaly, constitutional symptoms, and shortened survival. Data pertaining to the clinical characteristics and treatment patterns of patients with low-risk MF are limited; most studies have focused on patients with intermediate- and high-risk MF. The ongoing Myelofibrosis and Essential Thrombocythemia Observational STudy (MOST) was designed to characterize the demographics, disease burden, patient-reported outcomes, and management of patients with MF or essential thrombocythemia (ET) in clinical practices throughout the United States (NCT02953704). This analysis describes demographic and clinical characteristics of patients with low-risk MF enrolled in MOST. Methods: MOST is an ongoing multicenter, non-interventional, longitudinal, prospective, observational study in patients with MF or ET. Eligible patients with MF were at least 18 years old and had low- or intermediate-1 (INT-1) risk by age alone according to the Dynamic International Prognostic Scoring System (DIPSS). Patients participating in blinded investigational drug trials, having life expectancy ≤6 months, or having other concurrent myeloid malignancies were excluded. Data from patient records were entered into an electronic case report form during usual-care visits over a planned 36-month observation period. Data were analyzed with descriptive statistics. Results: A total of 232 patients with MF were enrolled between November 29, 2016 and March 29, 2019 at 124 sites. Two-hundred patients with low-risk (n=77) or INT-1 risk by age alone (n=123) MF were included in this analysis (data cut-off date, June 17, 2019); 32 patients were excluded due to incorrect risk categorization (n=27) or unanswered prognostic factors at enrollment (n=5). At enrollment, the median age was 68 (range, 35-88) years, 58% were aged >65 years, 49% were women, and 89% were white. Thirteen patients (7%) had a documented family history of MF, ET, or polycythemia vera. Of 157 patients with manual spleen assessment at enrollment, 55 (35%) had palpable splenomegaly; median spleen length was 7 (range, 1‒22) cm in 35 patients with available measurements. The median time from MF diagnosis to enrollment was 1.7 (range, 0.0-37.7) years; most patients (75%) were diagnosed within 5 years of enrollment. Of patients with available data, 93% (185/200) were reported to have undergone BM biopsy/aspiration and 82% (162/198) had mutation testing (MT) at the time of diagnosis; most patients had received both BM biopsy and MT (151/196 [77%]). Data from MT conducted prior to or within 30 days of diagnosis were available for 142 patients (71%); 134/142 patients (94%) were tested for a JAK2 mutation, of whom 95/134 (71%) were positive (Table 1). At enrollment, approximately half of patients with available data (97/190 [51%]) had hemoglobin below normal range, and approximately one-third had platelets (68/188 [36%]) or leukocytes (58/186 [31%]) above normal range (Table 2). The most common signs reported at the time of enrollment included lactate dehydrogenase greater than the upper limit of normal (41%), palpable spleen (31%), and leukocytosis (>11 × 109/L; 24%). Across both risk groups, 111 patients (56%) were receiving MF-directed monotherapy at enrollment (low-risk, 43/77 [56%]; INT-1 by age alone, 68/123 [55%]). Low-risk patients received hydroxyurea (HU; 23/43 [54%]), ruxolitinib (15/43 [35%]), interferon (4/43 [9%]), or anagrelide (1/43 [2%]); INT-1 patients received ruxolitinib (30/68 [44%]), HU (28/68 [41%]), interferon (8/68 [12%]), or anagrelide (2/68 [3%]). Five patients (3%) were receiving >1 MF-directed therapy. Less than half of low- (34/77 [44%]) and INT-1- (50/123 [41%]) risk patients were receiving no MF-directed therapy at enrollment. Conclusion: These real-world data provide insight into the clinical characteristics, diagnosis, and treatment patterns of patients with low- or INT-1 risk (by age alone) MF in the United States. Data from this trial will help characterize the rate at which patients transition from low- or INT-1-risk disease to higher risk categories of disease and how management is affected by disease progression. Disclosures Gerds: Sierra Oncology: Research Funding; Imago Biosciences: Research Funding; Incyte: Consultancy, Research Funding; Celgene Corporation: Consultancy, Research Funding; CTI Biopharma: Consultancy, Research Funding; Pfizer: Consultancy; Roche: Research Funding. Lyons:Texas Oncology: Equity Ownership; Amgen: Consultancy; McKesson: Other: Leadership. Colucci:Incyte: Employment, Equity Ownership. Kalafut:Incyte: Employment, Equity Ownership. Paranagama:Incyte: Employment, Equity Ownership. Verstovsek:Promedior: Research Funding; Blueprint Medicines Corp: Research Funding; CTI BioPharma Corp: Research Funding; Genetech: Research Funding; Pragmatist: Consultancy; Pharma Essentia: Research Funding; Astrazeneca: Research Funding; Ital Pharma: Research Funding; Protaganist Therapeutics: Research Funding; Constellation: Consultancy; Incyte: Research Funding; Roche: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Research Funding; Gilead: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Research Funding.

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