Hemorrhage in patients with polycythemia vera receiving aspirin with an anticoagulant: a prospective, observational study.

Polycythemia vera (PV) is associated with increased risk of thrombosis and hemorrhage. Aspirin, recommended for primary thromboprophylaxis, is often combined with anticoagulants during management of acute thrombotic events. The safety of dual antiplatelet and anticoagulant therapy is not established in PV. In a prospective, observational study, 2,510 patients with PV were enrolled at 227 sites in the United States. Patients were monitored for the development of hemorrhage and thrombosis after enrollment. A total of 1,602 patients with PV received aspirin with median follow-up of 2.4 years (range, 0-3.6 years). The exposure-adjusted rate of all hemorrhages in patients receiving aspirin alone was 1.40 per 100 patient-years (95% confidence interval [CI]: 0.99-1.82). The combination of aspirin plus anticoagulant was associated with an incidence of hemorrhage of 6.75 per 100 patient-years (95% CI: 3.04-10.46). The risk of hemorrhage was significantly greater in patients receiving the combination of aspirin and anticoagulant compared with aspirin alone (total hemorrhages, hazard ratio [HR]: 5.83; 95% CI: 3.36-10.11; P<0.001; severe hemorrhage, HR: 7.49; 95% CI: 3.02-18.62; P<0.001). Periods of thrombocytosis (>600×109/L) were associated with an increased risk of hemorrhage (HR: 2.25; 95% CI: 1.16- 4.38; P=0.02). Rates of hemorrhage were similar for aspirin in combination with warfarin or direct-acting oral anticoagulants. We conclude that the combination of aspirin and anticoagulants is associated with significantly increased risk of hemorrhage in patients with PV (clinicaltrials gov. Identifier: NCT02252159).

Real-world risk assessment and treatment initiation among patients with myelofibrosis at community oncology practices in the United States.

Myelofibrosis (MF) is a chronic myeloproliferative neoplasm with a prevalence of 4 to 6 per 100,000 people in the USA. Treatment recommendations are risk-adapted. This study was conducted to evaluate how physicians risk-stratify patients at the time of MF diagnosis, the accuracy of the risk stratification, and its effect on treatment selection. Medical charts were reviewed at US community hematology/oncology practices in the Cardinal Health Oncology Provider Extended Network; patient clinical characteristics, risk stratification, and treatment data were collected. Physician-assigned risk categorizations were compared with data-derived risk categorizations based on the International Prognostic Scoring System, the system recommended at diagnosis. A total of 491 patients diagnosed with MF between 2012 and 2016 (mean [SD] age at diagnosis, 65.4 [11.8] years; 54.8% male, 69.2% with primary MF) were included. Risk categorization was not assigned for 30.1% of patients. Of the patients with a physician-assigned risk categorization (n = 343), a scoring system was used in 49.9%. Compared with data-derived risk categorizations, 42.9% of physician-assigned risk categorizations were incorrect; 85.0% of incorrect physician-assigned risk categorizations were underestimations. Notably, 38.5% of patients with data-derived intermediate- or high-risk categorizations did not initiate treatment within 120 days of diagnosis. Among patients with data-derived intermediate risk, those with an underestimated physician-assigned risk categorization were significantly less likely to receive treatment within 120 days of diagnosis (51.6% with correct physician-assigned categorization vs 18.5% with underestimated risk categorization; P = 0.0023). These results highlight the gap in risk assessment and the importance of accurate risk stratification at diagnosis.

Disease and Clinical Characteristics of Patients With a Clinical Diagnosis of Myelofibrosis Enrolled in the MOST Study.

BACKGROUND: Clinical characteristics and treatment patterns of patients with lower-risk myelofibrosis (MF) are not well described. This analysis from the MOST (NCT02953704) assessed the demographic and clinical characteristics and treatment patterns of patients with the clinical diagnosis of lower-risk MF at enrollment. PATIENTS AND METHODS: MOST is an ongoing, prospective, observational study in patients with clinical diagnoses of MF or essential thrombocythemia enrolled at clinical practices throughout the United States. Patients included in the MF cohort (≥18 years of age) had low-risk MF by the Dynamic International Prognostic Scoring System or intermediate-1 (INT-1) risk MF (by age >65 years only) at enrollment. Patient data were entered into an electronic case report form during usual-care visits over a planned 36 month observation period. RESULTS: Two hundred five patients were eligible for this analysis (low risk, n = 85; INT-1 risk, n = 120; median age, 68 years [range, 35-88]); 166 patients (81.0%) had mutation testing results available. The median time from MF diagnosis to enrollment was 1.8 years. Hemoglobin and hematocrit levels were below the normal range in 50.5% and 48.7% of patients, respectively. Nearly all (98.0%) patients had comorbid conditions, most commonly hypertension (49.8%). Fatigue was the most common physician-reported MF symptom (30.7%). At enrollment, 55.6% of patients were receiving MF-directed monotherapy, most frequently hydroxyurea (46.5%) or ruxolitinib (40.4%). CONCLUSION: Future longitudinal analyses of data from MOST will help identify unmet needs and characterize how patients with lower-risk MF are managed throughout the disease course.

Safety and Efficacy of Ruxolitinib in Patients with Myelofibrosis and Low Platelet Counts (50 - 100 × 109/L): Final Analysis of an Open-Label Phase 2 Study.

INTRODUCTION: Treatment options in patients with myelofibrosis (MF) presenting with thrombocytopenia are limited. Final results of the phase 2 study (NCT01348490) of ruxolitinib in patients with MF and low baseline platelet counts (50 - 100 × 109/L) are reported. PATIENTS AND METHODS: Patients received ruxolitinib 5 mg twice daily (BID), with optional up-titration to a maximum of 15 mg BID, provided platelet count remained ≥40 × 109/L. Assessments included spleen volume and length, Total Symptom Score (TSS), quality of life, and safety. RESULTS: Of 66 patients, 52 (78.8%) completed the first 24 weeks of treatment. Median (range) percentage change from baseline in spleen volume and TSS (coprimary endpoints) were -20.5% (-55.8% to 38.5%, n=51) and -39.8% (-98.6% to 226.4%, n=53), respectively; greatest median reductions were in the 10 mg BID final titrated dose group. Of patients achieving ≥35% or ≥10% reduction in spleen volume, 8/11 (72.7%) and 21/34 (61.8%), respectively, were in the 10 mg BID final titrated dose group. Thirty-seven of 65 patients (56.9%) had ≥20% improvement in TSS, and 35/66 patients (53.0%) were Patient Global Impression of Change responders. Treatment-emergent adverse events led to dose interruption in 17/66 patients (25.8%), most commonly thrombocytopenia (n=3). CONCLUSION: A starting dose of ruxolitinib 5 mg BID with gradual up-titration and dose optimization based on hematologic parameters and response was efficacious and generally well-tolerated in patients with MF and low platelet counts. Median improvement in spleen volume and symptoms was greatest for patients receiving ruxolitinib 10 mg BID.

Real-World Dosing Patterns of Ruxolitinib in Patients With Polycythemia Vera Who Are Resistant to or Intolerant of Hydroxyurea.

INTRODUCTION: Approximately one-quarter of patients with polycythemia vera become resistant to and/or intolerant of hydroxyurea. This analysis characterizes reasons patients were switched from hydroxyurea to ruxolitinib and describes ruxolitinib dosing patterns and outcomes in real-world clinical practice. PATIENTS AND METHODS: This medical chart review of United States community hematology/oncology practices in the Cardinal Health Oncology Provider Extended Network included patients with polycythemia vera who were ≥18 years old, received hydroxyurea for ≥3 months, started ruxolitinib between January 1, 2015 and December 31, 2016, and had ≥2 visits during the subsequent 6 months. Clinical data were collected at predefined intervals from diagnosis to last provider visit. RESULTS: Providers identified 249 patients for inclusion. jcauses of hydroxyurea discontinuation were resistance (78%; frequently for hematocrit ≥45% [79%]) and intolerance (28%; frequently for nausea/vomiting [50%]). Initial ruxolitinib dosing was 10 mg twice daily (recommended dose) in 131 patients (53%). Among these patients, median treatment duration was 29.2 months, 35 (27%) had dose modification (increase, n = 24; decrease, n = 11) and 4 had interruptions within 6 months. The most common reason for dose increase was continued need for phlebotomy (46%); 6 patients had dose reductions owing to reduced platelets. Hematocrit control at initiation and during the first 6 months of ruxolitinib treatment was 15% and 63%, respectively. CONCLUSION: Most patients initiated ruxolitinib upon hydroxyurea resistance. Approximately half initiated ruxolitinib at the recommended dose, 27% of whom experienced dosing modifications within the first 6 months. After switching to ruxolitinib, most patients achieved hematocrit control and continued treatment for extended time frames.

Disease and Clinical Characteristics of Patients With a Clinical Diagnosis of Essential Thrombocythemia Enrolled in the MOST Study.

Few data exist regarding the disease and clinical characteristics of patients with essential thrombocythemia (ET) in the United States. The ongoing, multicenter, noninterventional, prospective, Myelofibrosis and Essential Thrombocythemia Observational STudy (MOST) was designed to collect data pertaining to the demographics, clinical management, and patient-reported outcomes in patients with myelofibrosis or ET in the United States (NCT02953704). This analysis examines the clinical characteristics of patients with clinical diagnoses of high-risk or low-risk ET receiving ET-directed therapy at enrollment. At data cutoff (June 17, 2019), 1207 of 1234 enrolled patients were eligible for this analysis (median age, 70 years; 65% female; 88% white); 917 patients (76%) had mutation testing results available. The median time from ET diagnosis to study enrollment was 4.2 years. The majority of patients (87%) had high-risk ET. Of 333 patients with a history of thrombotic events, 247 had at least 1 event classified as arterial and/or venous. Platelet count was above normal range in 54% of patients. Hypertension (56%) was the most common comorbidity. At enrollment, the majority of patients (low-risk ET, 94%; high-risk ET, 79%) were receiving ET-directed monotherapy. Additional prospective analyses from MOST will help to identify areas of unmet need.

Treatment Patterns and Blood Counts in Patients With Polycythemia Vera Treated With Hydroxyurea in the United States: An Analysis From the REVEAL Study.

BACKGROUND: Polycythemia vera (PV) is associated with increased blood cell counts, risk of thrombosis, and symptoms including fatigue and pruritus. National guidelines support the use of hydroxyurea (HU) in high-risk patients or those with some other clinical indication for cytoreduction. PATIENTS AND METHODS: REVEAL is a prospective, observational study designed to collect data pertaining to demographics, disease burden, clinical management, patient-reported outcomes, and health care resource utilization of patients with PV in the United States. In this analysis, HU treatment patterns and outcomes were assessed from 6 months prior to enrollment to the time of discontinuation, death, or data cutoff. RESULTS: Of the 1381 patients who received HU for ≥ 3 months, the median HU exposure was 23.6 months (range, 3.1-38.5 months). The most common maximum daily HU doses were 1000 mg (30.6%) and 500 mg (30.1%); only 6.4% received ≥ 2 g/d HU. Approximately one-third (32.3%) of patients had dose adjustments, 23.8% had dose interruptions, and 257 (18.6%) discontinued HU. The most common reasons for HU discontinuations and interruptions were adverse events/intolerance (37.1% and 54.5%, respectively) and lack of efficacy (35.5% and 22.1%, respectively). Of those who received HU for ≥ 3 months, 57.1% had hematocrit values > 45% on ≥ 1 occasion, 33.1% continued to receive phlebotomies, and 27.4% had uncontrolled myeloproliferation. CONCLUSION: The results of this analysis emphasize the need for active management of patients with PV with appropriate HU dose titration to maintain blood count control while monitoring for signs and symptoms of HU intolerance.

Symptom Burden and Blood Counts in Patients With Polycythemia Vera in the United States: An Analysis From the REVEAL Study.

BACKGROUND: Approximately 50% of patients with polycythemia vera (PV) have PV-related symptoms at diagnosis; these symptoms might develop or worsen with time. Symptoms have been shown to negatively affect quality of life and interfere with daily activities. To our knowledge, an analysis to evaluate the relationship between blood count control and symptoms has not been published. PATIENTS AND METHODS: The Prospective Observational Study of Patients with Polycythemia Vera in US Clinical Practices (REVEAL; NCT02252159) is a multicenter, noninterventional, nonrandomized prospective observational study of patients with PV in the United States. Patients included were required to have a complete blood count result within 30 days before completing the at-enrollment Myeloproliferative Neoplasm Self-Assessment Form Total Symptom Score (MPN-SAF TSS). Symptom severity was compared between those who had blood count control versus those who did not. RESULTS: At the time of enrollment, 1714 patients (94.5%) were being managed with cytoreductive therapy; 468 patients (25.8%) had complete hematologic remission (CHR), 1614 patients (89.0%) had ≥1 controlled blood count, and 1122 patients (61.9%) had ≥2 controlled blood counts. Mean MPN-SAF TSSs were similar across patients in different blood count control groups. Fatigue was the most frequently reported symptom. The severity of individual symptoms, except those of pruritus and night sweats, was not affected by CHR or the number of blood counts that were controlled. CONCLUSION: Symptom burden in patients with PV can persist despite control of blood counts, which suggests some discordance between laboratory values and symptom burden. Consequently, regular monitoring of symptom burden should be factored into the assessment of disease control.

Are patients with high-risk polycythemia vera receiving cytoreductive medications? A retrospective analysis of real-world data.

BACKGROUND: Patients with polycythemia vera (PV) have a higher mortality risk compared with the general population, primarily driven by cardiovascular disease, thrombotic events (TEs), and hematologic transformations. The goal of risk-adapted therapy in PV is prevention of TEs. Current treatment recommendations indicate that high-risk patients (aged ≥ 60 years and/or with history of TEs) should be managed with cytoreductive medications, phlebotomy, and low-dose aspirin. This noninterventional study was conducted to describe real-world cytoreductive medication treatment in adult patients with PV, stratified by risk, in the United States. METHODS: This retrospective analysis used claims data from the Truven Health MarketScan® database. Inclusion criteria were ≥ 2 nondiagnostic claims for PV ≥ 30 days apart, age ≥ 18 years, continuous enrollment during the preindex period (January 1 to December 31, 2012), and continuous enrollment or death during the postindex period (January 1, 2013, to December 31, 2014). Assessments included patient demographics, clinical characteristics, and treatment with cytoreductive medications. RESULTS: A total of 2856 patients were identified for this analysis, including 1823 with high-risk PV and 1033 with low-risk PV. Mean (SD) age was 62.5 (13.5) years, and 65.9% of patients were male. Preindex comorbid conditions of interest were more common in high-risk than low-risk patients, including hypertension (65.0% vs 43.1%), type 2 diabetes (21.7% vs 10.1%), and congestive heart failure (6.6% vs 0.6%). Among patients who received preindex cytoreductive therapy, the most commonly used medications in high-risk (n = 666) and low-risk (n = 160) patients were hydroxyurea (94.7 and 87.5%, respectively), anagrelide (7.4 and 11.9%), and interferon (1.7 and 4.4%). Among patients who initiated cytoreductive therapy postindex, the most commonly used medications in high-risk (n = 100) and low-risk (n = 35) patients were hydroxyurea (97.0 and 91.4%, respectively), anagrelide (4.0 and 2.9%), and interferon (2.0 and 8.6%). Overall, 42.0% of high-risk and 18.9% of low-risk patients received cytoreductive medication during the preindex or postindex periods. CONCLUSIONS: Despite consistent guideline recommendations for cytoreductive therapy in patients with high-risk PV, this analysis revealed that only a minority of these patients received cytoreductive medication. A notable proportion of high-risk patients with PV would likely benefit from a revised treatment plan that aligns with current guidelines.

Clinical and Disease Characteristics From REVEAL at Time of Enrollment (Baseline): Prospective Observational Study of Patients With Polycythemia Vera in the United States.

BACKGROUND: Polycythemia vera (PV) has a prevalence of 44 to 57 per 100,000 people in the United States. Prospective data concerning the demographics, clinical characteristics, and treatment patterns of patients with PV in the United States are lacking. PATIENTS AND METHODS: The ongoing, prospective, observational REVEAL study evaluates demographics, disease burden, clinical management, patient-reported outcomes, and health care resource utilization of adult patients with PV in the United States. This report summarizes the demographics and clinical characteristics of patients at enrollment (baseline). RESULTS: Patients (n = 2510) were a median age of 67.0 years, 54.2% were male, and 89.1% were white. The median time from PV diagnosis to study enrollment was 4.0 (range, 0-56.3) years. Most patients (89.7%) were diagnosed after an abnormal blood test. Less than half (49.2%) underwent JAK2 mutation analysis, of whom 95.8% were JAK2 V617F mutation positive; < 1% were positive for JAK2 exon 12 mutations. At enrollment, 47.7% of patients had elevated hematocrit (> 45%), 35.8% had elevated platelets (> 400 × 109/L), and 37.0% had elevated leukocytes (> 10 × 109/L). Most patients (94.5%) were receiving active PV treatment, predominantly therapeutic phlebotomy alone (33.6%), hydroxyurea monotherapy (29.0%), or hydroxyurea plus phlebotomy (23.7%). Thrombotic events occurred in 11.9% of patients before PV diagnosis (venous, 6.7%; arterial, 5.7%), and 8.3% between diagnosis and enrollment. Hypertension (70.6%) was the most common previous medical condition. CONCLUSION: REVEAL enrollment data inform our understanding of the baseline demographics, diagnostic approach, disease characteristics, and treatment patterns of patients with PV in the United States. Longitudinal real-world data collected in this study will complement information collected during randomized controlled clinical trials.

Patient-Reported Outcomes Data From REVEAL at the Time of Enrollment (Baseline): A Prospective Observational Study of Patients With Polycythemia Vera in the United States.

BACKGROUND: Patients with polycythemia vera (PV) often experience symptoms that adversely affect their quality of life (QoL). The ongoing, prospective, observational REVEAL (Prospective Observational Study of Patients With Polycythemia Vera in US Clinical Practices) study was designed to collect contemporary data regarding burden of disease, clinical management, patient-reported outcomes (PROs), and health care resource utilization from adult patients with PV in the United States. PATIENTS AND METHODS: Data on PROs were collected at enrollment using the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS; range, 0-100); the European Organization for Research and Treatment of Cancer-Core Quality of Life Questionnaire, version 3.0 (EORTC QLQ-C30; range, 0-100); and the Work Productivity and Activity Impairment Questionnaire-Specific Health Problem (WPAI-SHP; range, 0%-100%). RESULTS: Among 2309 patients, mean (SD) disease duration was 5.8 (6.1) years and Charlson Comorbidity Index was 3.4 (0.8); 54.0% (1247/2309) were male. Mean (SD) MPN-SAF TSS was 18.8 (15.5). The most common symptoms were fatigue (80.1% [1844/2302]), early satiety (60.9% [1402/2302]), and inactivity (57.6% [1324/2302]). The most common severe symptoms were fatigue (16.8% [387/2302]), itching (13.4% [308/2302]), and inactivity (11.8% [271/2302]). The mean (SD) EORTC QLQ-C30 global health status/QoL score was 73.1 (23.2): mean functional subscale scores ranged from 80.5 (23.9) for cognitive functioning to 85.7 (24.6) for social functioning. The mean WPAI-SHP activity impairment score was 19.7% (n = 2300). Employed patients had mean WPAI-SHP scores for absenteeism, presenteeism, and overall work impairment of 3.2% (n = 810), 12.1% (n = 807), and 13.4% (n = 802), respectively. CONCLUSION: These data confirm that many patients with PV experience symptoms, QoL impairments, and work productivity impairments that negatively affect their lives. Longitudinal data from REVEAL will be important for evaluating how PROs change over time in these patients.

Some aspects of the endocrine profile and management of hormone-dependent male breast cancer.

The management of hormone-dependent male breast cancer is insufficiently understood by practicing oncologists. This article provides a review of the endocrine profile of male breast cancer, and outlines the differences between hormone-dependent female and male breast cancers. A concise review of the past, present, and possible future management of hormone-dependent male breast cancer is presented. For a better understanding of this disease, more information on the natural history and biological behaviors of patients with male breast cancer is needed. This could be accomplished by the development of a specific multi-institutional tumor registry and execution of prospective clinical trials.

Comparison of healthcare utilization and direct costs in three degenerative dementias.

The authors conducted a survey of healthcare utilization in three dementia syndromes to determine whether type of dementia influenced utilization or resulting direct costs. Patients with Alzheimer disease (n=131), dementia with parkinsonism (n=85), and Huntington disease (n=51) were identified from a registry and enrolled. Caregivers completed the mailed survey, and direct costs were estimated. The presence of dementia with parkinsonism resulted in significantly greater utilization of long-term care services and higher total direct costs. In all three groups, long-term care costs accounted for the majority of direct costs. Unique patterns of utilization and costs are seen in specific neurodegenerative dementias.