Parasuraman, Shreekant

Abstract Background Previous studies report increasing cholangiocarcinoma (CCA) incidence up to 2015. This contemporary retrospective analysis of CCA incidence and mortality in the US from 2001-2017 assessed whether CCA incidence continued to increase beyond 2015. Patients and Methods Patients (≥18 years) with CCA were identified in the National Cancer Institute Surveillance, Epidemiology, and End Results 18 cancer registry (International Classification of Disease for Oncology [ICD-O]-3 codes: intrahepatic [iCCA], C221; extrahepatic [eCCA], C240, C241, C249). Cancer of unknown primary (CUP) cases were identified (ICD-O-3: C809; 8140/2, 8140/3, 8141/3, 8143/3, 8147/3) because of potential misclassification as iCCA. Results Forty-thousand-and-thirty CCA cases (iCCA, n=13,174; eCCA, n=26,821; iCCA and eCCA, n=35) and 32,980 CUP cases were analyzed. From 2001-2017, CCA, iCCA, and eCCA incidence (per 100 000 person-years) increased 43.8% (3.08 to 4.43), 148.8% (0.80 to 1.99), and 7.5% (2.28 to 2.45), respectively. In contrast, CUP incidence decreased 54.4% (4.65 to 2.12). CCA incidence increased with age, with greatest increase among younger patients (18-44 years, 81.0%). Median overall survival from diagnosis was 8, 6, 9, and 2 months for CCA, iCCA, eCCA, and CUP. From 2001-2016, annual mortality rate declined for iCCA (57.1% to 41.2%) and generally remained stable for eCCA (40.9% to 37.0%) and for CUP (64.3% to 68.6%). Conclusions CCA incidence continued to increase from 2001-2017, with greater increase in iCCA versus eCCA, whereas CUP incidence decreased. The divergent CUP versus iCCA incidence trends, with overall greater absolute change in iCCA incidence, provide evidence for a true increase in iCCA incidence that may not be wholly attributable to CUP reclassification.

Abstract Background: Phlebotomy to maintain hematocrit <45% is considered one of the cornerstones for the management of polycythemia vera (PV). However, phlebotomy procedures may be inconvenient for or poorly tolerated by some patients, and often result in iron deficiency, which may be associated with additional quality-of-life burden, such as fatigue, impaired cognitive function and restless leg syndrome. The REVEAL study (ClinicalTrials.gov, NCT02252159) is being conducted to describe contemporary demographics, burden of disease, clinical management, patient-reported outcomes, and healthcare resource utilization among patients with PV in the US. This early analysis describes the patient self-reported burden of phlebotomy at the time of enrollment. Methods: REVEAL is a multicenter, noninterventional, nonrandomized, prospective, observational study of adult patients with PV who are currently under the care of a US physician. REVEAL collects physician assessments and patient-reported outcomes during a 36-month observation period. Phlebotomy-related burden is being assessed with a new 21-item phlebotomy burden questionnaire (PBQ-21) at enrollment and every 90 days thereafter; it assesses patient-reported phlebotomy frequency, practice setting, time required for phlebotomy, inconvenience, and phlebotomy-related adverse effects. Phlebotomy-related effects and bother/inconvenience (if experienced within 24 hours after a phlebotomy procedure) are graded on a 4-point scale of 1 (not at all) to 4 (extremely). Analyses of these preliminary data were descriptive. Results: At the time of data cutoff, 865 patients were enrolled (total planned enrollment, n=2000). Median age was 67 (range, 22-95) years, 55.5% were male, and 89.5% were white. Median time from PV diagnosis to study enrollment was 53 months. Overall, 748 patients completed the PBQ-21 at enrollment and 400 (53.5%) had received a phlebotomy within 3 months prior to enrollment. Mean number of phlebotomies in the past 3 months was 2.2 (SD, 1.7). Phlebotomy was most commonly performed at a doctor's office during a regular medical visit (37.8%), at an infusion center or special cancer care center (26.8%), or at a hospital (18.3%). Patients who had phlebotomy procedures within 90 days before enrollment reported a mean total treatment time of 4.2 (SD, 4.7) hours per phlebotomy procedure; for employed patients, the mean amount of work time missed was 4.6 (SD, 15.6) hours per procedure. Fatigue, bruising, dehydration, and dizziness were among the most commonly reported adverse effects of phlebotomy (Table 1). Twenty percent of patients reported that phlebotomy procedures were moderately or extremely bothersome, inconvenient (18.3%), or painful or physically uncomfortable (16.3%). Furthermore, some patients (8.8%) reported that their family and friends were moderately or severely inconvenienced by phlebotomy procedures. Conclusion: The PBQ-21 collects important and relevant patient-reported information to systematically assess the impact of phlebotomy on patients and caregivers. From the early view of REVEAL enrollment data, a considerable proportion of patients reported fatigue, bruising, dehydration, and dizziness resulting from phlebotomy procedures. Furthermore, patients reported spending a considerable amount of time (4 hours on average) per phlebotomy procedure, which is a sizeable burden for patients who are employed. In addition, some patients reported that phlebotomy procedures may be inconvenient, painful or uncomfortable, and bothersome. REVEAL provides important information for providers to understand and address when to prescribe phlebotomy for patients with PV. Disclosures Boccia: Incyte Corporation: Honoraria. Stein:Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees. Mesa:Genentech: Research Funding; Promedior: Research Funding; NS Pharma: Research Funding; CTI Biopharma: Research Funding; Gilead: Research Funding; Incyte Corporation: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Pfizer: Research Funding. Naim:Incyte Corporation: Employment, Equity Ownership. Cordaro:Incyte Corporation: Employment, Equity Ownership. Peng:Incyte Corporation: Employment, Equity Ownership. Sun:Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Moliterno:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees.

Abstract Background: Phlebotomy is a common and established treatment in patients diagnosed with polycythemia vera (PV) to reduce the risk of thromboembolic events, in both acute and chronic settings. However, phlebotomy may not alleviate all PV-related symptoms and its frequent application can cause moderate to profound iron deficiency, which may worsen PV-related symptoms. This analysis of MPN Landmark survey data examined patient-reported quality of life (QoL) and productivity outcomes in patients with PV based on phlebotomy treatment history. Methods: Patients who were diagnosed with a myeloproliferative neoplasm (MPN) were recruited to participate in the MPN Landmark survey in the US (fielded May - July 2014). This analysis describes responses from patients with PV on questions regarding PV-related symptom burden, QoL, and productivity. Patient responses were analyzed based on phlebotomy treatment history and included patients who were actively receiving phlebotomy within the last 3 months (≥1 per month, every other month, and every 3 months or longer), had discontinued phlebotomy, or were phlebotomy-naive. Descriptive statistical analyses were used to evaluate these outcomes based on phlebotomy frequency, as appropriate. Results: Overall, 813 patients completed the Landmark survey, and 274 out of the 380 patients with PV who completed the survey were evaluable for this analysis. Mean age ranged from 61.6-65.4 years among phlebotomy subgroups (Table 1). The average duration of PV was longest among patients with PV who had discontinued phlebotomy (12.0 years) compared with phlebotomy-naive patients (6.3 years) and patients actively treated with phlebotomy (5.9-8.9 years). The percentage of patients diagnosed within 1 year of the survey ranged from 4.1% to 11.5% among the patients who had been treated with phlebotomy and was 15.4% in the phlebotomy-naive subgroup. Most patients reported PV-related symptoms; symptom burden was similar in all phlebotomy subgroups. Fatigue was the most common symptom reported in all subgroups (range, 71.4%-80.8%). QoL measures were generally worse with higher phlebotomy frequency (Table 1). Similarly, more frequent phlebotomy procedures was found to be associated with reduced productivity: patients who received ≥1 phlebotomy per month had the highest mean number (in the preceding 30 days) of sick days (among patients employed), days spent in bed, and days with plans canceled. Of note, approximately one third of patients receiving more frequent phlebotomy procedures were also receiving concomitant hydroxyurea to manage their PV (≥1 per month, 38.5%; every other month, 36.4%). Conclusion: Patients with PV may experience disease-related symptoms and reductions in QoL and work productivity. Frequent phlebotomy procedures were associated with increasingly worsened QoL and decreased work productivity. Further research is needed to better understand the impact of phlebotomy on patient-reported outcomes in patients with PV. Disclosures Fazal: Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Ariad: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Miller:Incyte Corporation: Honoraria, Research Funding. Mascarenhas:Promedior: Research Funding; Roche: Research Funding; CTI Biopharma: Research Funding; Kalobios: Research Funding; Novartis Pharmaceuticals Corporation: Research Funding; Incyte Corporation: Research Funding. Thyne:Incyte Corporation: Speakers Bureau. Paranagama:Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Naim:Incyte Corporation: Employment, Equity Ownership. Mangan:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Mesa:Promedior: Research Funding; Genentech: Research Funding; Gilead: Research Funding; NS Pharma: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; CTI Biopharma: Research Funding; Pfizer: Research Funding; Incyte Corporation: Research Funding.

Abstract Background: Patients with the myeloproliferative neoplasm (MPN) polycythemia vera (PV) require treatment to manage blood cell counts and reduce the risks of cardiovascular/thromboembolic events. Hydroxyurea (HU) is a common cytoreductive treatment; however, some patients discontinue HU treatment because of resistance, intolerance, or frequently a combination of both limitations. Patients may also continue to receive HU despite diminishing or nonexistent clinical benefit, sometimes in combination with persistent need for phlebotomy procedures. This analysis of MPN Landmark survey data examined patient-reported quality of life (QoL) outcomes in patients with PV who were naive to HU (HU-N), were continuing HU (HU-C), or had discontinued HU (HU-D). Methods: Patients with an MPN under active management in the US were eligible to complete an online survey (fielded May - July 2014). This is a report of responses given by patients with PV to questions about symptom burden, QoL, activities of daily living (ADL), and work/productivity. PV-related effects on patients feeling depressed/discouraged, patients feeling anxious/worried, or interference with ADLs were considered to be at high levels if the patient-reported score was ≥4 on a scale of 1 (not at all) to 5 (a great deal). Symptom severity was rated on a scale of 0 (absent) to 10 (worst imaginable). Results: The survey respondents included 380 patients with PV (HU-N, n=159; HU-C, n=181; HU-D, n=40). Mean age was 62.2 years, 65.1 years, and 64.2 years in the HU-N, HU-C, and HU-D groups, respectively. Mean duration of PV was 8.3 years, 10.3 years, and 13.9 years in the HU-N, HU-C, and HU-D groups, respectively. Patients who had not received HU were currently or previously treated with phlebotomy (87.4%), interferon (11.3%), or anagrelide (9.4%); 66.0% of HU-N patients were classified as high-risk based on information provided by the patients in the survey (ie, age 60 or older or history of thrombosis). Among HU-C and HU-D patients, treatment history included phlebotomy (89.5% and 100%, respectively), interferon (7.2% and 52.5%), or anagrelide (15.5% and 35.0%); 79.6% and 82.5%, respectively, were classified as high-risk. Ruxolitinib was not FDA-approved for PV at the time of this survey. Patients reported high levels of feeling anxious/worried and depressed/discouraged as a result of their PV across all subgroups: HU-N, 27.7% and 15.1%, respectively; HU-C, 22.7% and 15.5%; HU-D, 32.5% and 22.5%. Many patients also experienced a high level of PV-related interference with ADLs, which was more common in the HU-D group (30.0%) than the HU-N (11.3%) or HU-C (18.2%) groups. HU-D patients were more likely to have reported ever reducing their work hours (54.2% of the patients who responded) compared with the HU-N (33.3%) and HU-C groups (36.8%). Among all patients, HU-D patients reported a mean of 8.3 doctor visits in the past 12 months, compared with 5.6 in the HU-N group and 6.6 in the HU-C group. Most patients had experienced PV-related symptoms in the past 12 months (Table 1), particularly fatigue, itching, and day/night sweats; fatigue was ranked first as the symptom that patients would most like to resolve. Conclusion: Patients with PV in a large retrospective real-world survey across the US are found to experience burdensome PV-related symptoms and reduced QoL. The findings from this study also show that standard treatments do not address these aspects of PV in many patients, and patients who have discontinued HU may experience an even greater disease burden, possibly because of a lack of effective and/or safe alternative treatment options. Importantly, while 66.0% of the patients in the HU-N group were classified as high-risk, the majority of the high-risk patients in the HU-N group (81.0%) were not treated with cytoreductive agents, suggesting a potential knowledge deficit regarding recommendations for PV management. Collectively, these results illustrate the adverse impact of PV-related symptom burden on patient QoL and reinforce the importance of unmet control of PV-related symptoms in choosing PV therapy. Disclosures Mesa: Novartis Pharmaceuticals Corporation: Consultancy; NS Pharma: Research Funding; Pfizer: Research Funding; Genentech: Research Funding; CTI Biopharma: Research Funding; Incyte Corporation: Research Funding; Promedior: Research Funding; Gilead: Research Funding. Miller:Incyte Corporation: Honoraria, Research Funding. Mascarenhas:Promedior: Research Funding; Roche: Research Funding; CTI Biopharma: Research Funding; Incyte Corporation: Research Funding; Novartis Pharmaceuticals Corporation: Research Funding; Kalobios: Research Funding. Thyne:Incyte Corporation: Speakers Bureau. Paranagama:Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Fazal:Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Ariad: Consultancy, Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Naim:Incyte Corporation: Employment, Equity Ownership. Mangan:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees.

Abstract Background: Patients with myeloproliferative neoplasms (MPNs), including myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET), report high symptom burden that may compromise activities of daily living and quality of life. Results from the MPN Landmark survey suggest that for gainfully employed patients, disease symptoms may impact work productivity or career opportunities. The objective of this study was to assess the effects of MPNs on employment status, work productivity, and daily activities of patients in the United States. Methods: Adult patients (18-70 years) diagnosed with MF, PV, or ET participated in an online survey conducted between April and July 2016. The survey asked about diagnosis, disease-related history, MPN-related symptoms, functional status, changes in employment status since diagnosis due to MPNs, and work productivity (assessed using the Work Productivity and Activity Impairment Specific Health Problem Questionnaire, WPAI-SHP V2). Descriptive statistics were used to report MPN-related symptoms, employment changes, and WPAI scores for patients with MPNs who were employed at diagnosis and currently. Results: A total of 595 patients (MF, n=148; PV, n=284; ET, n=163) completed the survey, with 387 (65.0%) employed full- or part-time at diagnosis (MF, n=90; PV, n=178; ET, n=119). Among patients who were employed at diagnosis, mean (SD) age was 54.3 (10.5) years, 70.0% were female, and 47.8% had a bachelor's degree or higher. Mean (SD) duration of disease was 6.4 (6.6) years. After diagnosis, almost half of the patients (49.9%) experienced ≥1 change in employment resulting from their MPN, one-third (34.1%) had ≥2 different types of changes, and almost one-quarter (22.7%) had ≥3 different types of changes (Table). Almost one-third of patients (31.3%) reported 'leaving a job' due to their condition, which was also the most common employment change. The mean (SD) time from diagnosis to first job change due to MPN disease was 2.4 (5.2) years. Among those currently employed, the mean percentage of overall effects on work productivity due to MPNs were 29.3% for work impairment (MF, 28.4%; PV, 30.0%; ET, 28.6%), 25.7% for impairment while at work (presenteeism; MF, 22.1%; PV, 26.5%; ET, 26.4%), and 6.4% for work time missed (absenteeism; MF, 9.4%; PV, 6.6%; ET, 4.9%). The mean (SD) number of hours of work missed per week was 2.0 (4.9). The mean percentage of daily activity impairment was 31.6% (MF, 32.1%; PV, 32.0%; ET, 30.8%). The effects of MPNs on work productivity and daily activities are similar to those reported by patients with other significant chronic conditions such as rheumatoid arthritis (work time missed, 19.1%; impairment while working, 24.0%; activity impairment; 33.3%; Bansback N, et al. Rheumatology. 2012;51:375-84). Conclusion: MPNs have a substantial negative impact on patients' employment status and work productivity. Half of the employed patients with MPNs surveyed had a change in employment status (eg, leaving job, medical disability leave, early retirement) due to their disease. Moreover, currently employed patients reported a meaningful loss in work productivity due to their MPNs. Disclosures Yu: Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Paranagama:Incyte Corporation: Employment, Equity Ownership. Naim:Incyte Corporation: Employment, Equity Ownership. Dubinski:Incyte Corporation: Employment, Equity Ownership. Bai:Incyte Corporation: Employment, Equity Ownership. Mesa:Novartis: Consultancy; Galena: Consultancy; Ariad: Consultancy; Incyte Corporation: Research Funding; Promedior: Research Funding; Gilead: Research Funding; Celgene: Research Funding; CTI: Research Funding.

Abstract Background: Patients with polycythemia vera (PV) can have a pronounced symptom burden that negatively impacts their quality of life (QoL). Traditional treatment options such as phlebotomy, hydroxyurea, and interferon provide clinical benefit but frequently do not alleviate symptoms. The ongoing REVEAL study is being conducted to describe contemporary demographics, burden of disease, clinical management, patient-reported outcomes, and healthcare resource utilization among patients with PV in the US. This preliminary analysis describes the burden of PV based on patient-reported outcomes (PROs), including health-related QoL and work productivity. Methods: REVEAL is a multicenter, noninterventional, nonrandomized, prospective, observational study. Eligible patients are ≥18 years of age with a PV diagnosis and currently under active management by a physician in the US. PROs are being collected at study enrollment and every 3 months thereafter. Each of the 10 items on the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) are graded from 0 (absent) to 10 (worst imaginable), with individual symptom scores ≥7 considered severe; total symptom score (TSS) ranges from 0-100. Raw scores for items on the 30-item European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (EORTC QLQ-C30) are standardized by linear transformation to 0-100. Higher scores on the EORTC QLQ-C30 indicate better functioning for global health status/QoL and functional subscales and worse severity for symptom subscales. Outcomes with the 6-item Work Productivity and Activity Impairment Specific Health Problem questionnaire (WPAI-SHP) are presented as a proportion from 0% (minimal/no impairment) to 100% (maximal impairment/productivity loss). Analyses of these preliminary data were descriptive. Results: At the time of data cutoff (June 9, 2015), REVEAL had enrolled 865 patients (total planned enrollment, n=2000), the majority were male (55.5%) and white (89.5%), with a median age of 67 (range, 22-95) years. 782 patients had completed the PRO questionnaires at the enrollment visit. A majority of patients reported ≥1 PV-related symptom. Mean (SD) MPN-SAF symptom scores were highest for fatigue (3.5 [2.7]), early satiety (2.7 [2.8]), inactivity (2.7 [2.9]), itching (2.6 [3.1]), and concentration problems (2.1 [2.6]). The mean (SD) MPN-SAF TSS (sum of 10 symptom scores) was 19.6 (16.1). The most frequently reported severe symptoms were fatigue, itching, inactivity, early satiety, night sweats, concentration problems, and bone pain (Table 1). Mean (SD) global health status/QoL reported on the EORTC QLQ-C30 was 72.8 (23.4); functional subscales were as follows: cognitive functioning, 80.3 (24.5); emotional functioning, 80.7 (24.0); physical functioning, 83.1 (20.6); role functioning, 84.3 (26.1); and social functioning, 85.0 (25.0). The most severe mean (SD) symptom subscale scores were fatigue (30.7 [28.5]), insomnia (29.5 [34.5]), pain (20.9 [29.3]), and dyspnea (17.3 [28.6]). Among patients who were employed at baseline (n=273), mean (SD) PV-related WPAI-SHP scores were as follows: absenteeism (ie, work time missed), 2.9% (10.6%); presenteeism (ie, impairment at work/reduced on-the-job effectiveness), 10.7% (20.4%); work productivity loss (ie, absenteeism plus presenteeism), 12.0% (22.2%); and activity impairment, 21.0% (28.0%). Conclusion: Preliminary descriptive data from patients currently enrolled in REVEAL suggest that patients with PV have notable impairment in QoL because of their disease; patient-reported scores on the MPN-SAF and EORTC QLQ-C30 were similar to those reported previously for patient populations with MPNs. Similarly, PV is associated with marked work productivity loss among patients who are currently employed. Subsequent analyses from REVEAL will evaluate changes over time in PROs and investigate correlations with disease progression and treatment. REVEAL can provide novel insights into questions related to the contemporary real-world QoL burden and its impact on PV-related symptoms and work productivity. Disclosures Mesa: Pfizer: Research Funding; NS Pharma: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Incyte Corporation: Research Funding; CTI Biopharma: Research Funding; Promedior: Research Funding. Boccia:Incyte Corporation: Honoraria. Moliterno:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Naim:Incyte Corporation: Employment, Equity Ownership. Cordaro:Incyte Corporation: Employment, Equity Ownership. Peng:Incyte Corporation: Employment, Equity Ownership. Sun:Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Stein:Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Abstract Background: Myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET) are chronic myeloproliferative neoplasms (MPNs). Patients across all 3 MPNs experience marked disease burden in terms of symptoms and negative effects on quality of life (QoL), productivity, and activities of daily living (ADL). To improve the lives and health of patients with MPNs, it is also important to have a current understanding of these burdens from a financial standpoint. This analysis of MPN Landmark survey data examined the financial burden of patients who reported that their MPN affected their employment (ie, reduced work hours, discontinued employment, or went on medical disability) or experienced no such effects on their employment. Methods: Patients diagnosed with MF, PV, or ET were recruited to participate in a real-world retrospective study (MPN Landmark survey) in the US (fielded May - July 2014). Only respondents who were diagnosed before 2013 and were 16 to 65 years of age at the time of diagnosis were eligible for this analysis. Participants were asked if their MPN had an impact in terms of reduced work hours, discontinued employment, medical disability, or no impact; the first 3 categories were not mutually exclusive. Participants provided information on their annual household income in 2013 before taxes by selecting from the following categories: ≤$15,000, $15,001-$25,000, $25,001-$35,000, $35,001-$50,000, $50,001-$75,000, $75,001-$100,000, and >$100,000. The mid value of each range was used to calculate mean income levels within each subgroup evaluated. Results: A total of 813 patients completed the web-based Landmark survey and 369 eligible patients were included in this analysis (MF, 85; PV, 172; ET, 112). Median age among patients with ET was slightly lower than among patients with MF and PV at time of MPN diagnosis (ET, 48 years; MF, 56 years; PV, 53 years). The majority of respondents were women (MF, 62%; PV, 52%; ET, 75%). Almost all patients (99%) had health insurance, primarily group commercial insurance through an employer (MF, 46%; PV, 53%; ET, 57%) and Medicare (MF, 40%; PV, 34%; ET, 24%). Most patients had at least some college education (ie, some college, 4-year degree, or postgraduate degree): MF, 86%; PV, 90%; ET, 88%. The mean 2013 household income of patients with MF, PV, and ET were similar to each other ($79,800, $80,200, and $80,400, respectively) and slightly higher than the total 2013 US mean household income of $75,839. A notable proportion of patients in each MPN group reported that their disease led to reduced work hours, discontinued employment, and medical disability: MF, 38%, 35%, and 33%, respectively; PV, 33%, 28%, and 15%; ET, 28%, 21%, and 4%. Patient demographics, such as age and health insurance status, were similar among patients who reported MPN-associated effects on employment and patients who did not within each MPN. In each MPN group, the mean percentage household income loss in patients with reduced work hours, discontinued employment, and medical disability were: MF, 16%, 18%, and 28%, respectively; PV, 15%, 24%, and 17%; and ET, 0%, 24%, and 37%, compared with patients who did not experience any effects of their MPN on employment (Figure 1). Discontinued employment and medical disability tended to have a greater impact compared with reduced work hours across MPNs. Conclusion: Patients withMPNs may experience a considerable negative impact on their employment status, which in turn may be associated with reduced annual household income. Therefore, across all MPNs, forestalling or reversing discrete aspects of the diseases that negatively impact individual productivity is an important factor in the management of these chronic neoplasms. Disclosures Parasuraman: Incyte Corporation: Employment, Equity Ownership. Naim:Incyte Corporation: Employment, Equity Ownership. Paranagama:Incyte Corporation: Employment, Equity Ownership. Thyne:Incyte Corporation: Speakers Bureau. Mascarenhas:Incyte Corporation: Research Funding; Novartis Pharmaceuticals Corporation: Research Funding; Promedior: Research Funding; Roche: Research Funding; CTI Biopharma: Research Funding; Kalobios: Research Funding. Mangan:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Fazal:Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Ariad: Consultancy, Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Miller:Incyte Corporation: Honoraria, Research Funding. Mesa:Promedior: Research Funding; Gilead: Research Funding; Incyte Corporation: Research Funding; NS Pharma: Research Funding; CTI Biopharma: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Genentech: Research Funding; Pfizer: Research Funding.

Abstract Background: Patients with polycythemia vera (PV) have an increased symptom burden (eg, fatigue, pruritus, and splenomegaly-related symptoms) and an increased risk of mortality compared with the general population, often resulting from thrombotic events, disease transformation to myelofibrosis, or secondary malignancies. There are limited data regarding PV burden and treatment patterns in a contemporary, real-world US setting. REVEAL is an ongoing observational study being conducted to describe contemporary demographics, burden of disease, clinical management, patient-reported outcomes, and healthcare resource utilization among patients with PV in the US. The objective of this assessment is to describe the clinical characteristics at enrollment among patients currently enrolled in REVEAL (enrollment from July 22, 2014 to June 9, 2015). Methods: REVEAL is a multicenter, noninterventional, nonrandomized, prospective, observational study. Eligible patients are ≥18 years of age with a PV diagnosis and currently under active management by a physician in the US. Data regarding disease and clinical characteristics, patient-reported outcomes, and health resource utilization are being collected at usual-care visits over a planned 36-month observation period. Analyses of these preliminary data were descriptive. Results: At data cutoff, 865 patients were enrolled (total planned enrollment, n=2000) from 174 sites (academic, n=27; community, n=147). Median (range) age at enrollment was 67 (22-95) years, 55.5% were male, 89.5% were white, and 45.4% had a history of smoking. Most patients (99.4%) had health insurance, including Medicare (56.0%), PPO (24.3%), or HMO (11.6%). Fifty-two percent were retired, 29.6% were employed, and 4.5% were unable to work or disabled. A total of 40.2% of patients completed a college/graduate degree, 19.9% had some college, and 32.5% completed high school or the equivalent. Documented major World Health Organization diagnostic criteria included JAK2V617F mutation in 50.9% of patients, elevated hemoglobin in 52.3%, and red cell mass in 5.5%. A bone marrow biopsy was conducted in 24.0% of patients, approximately half of whom (52.4% of the 24.0%) had trilineage myeloproliferation. Erythropoietin levels were abnormal in 19.7% of patients. Approximately half (46.6%) of patients had physician-reported PV-related symptoms at diagnosis, most frequently fatigue (25.2%) and pruritus (14.0%). At enrollment, median disease duration was 52.6 months; 42.3% of patients were diagnosed ≥5 years before enrollment. The most common comorbidities were hypertension (51.3%), obesity (14.2%), dyspnea (13.4%), myalgia (11.2%), and diabetes mellitus (11.1%). Mean hematocrit was 44.9%, hemoglobin was 14.5 g/dL, white blood cell count was 11.4×109/L, platelet count was 363.7×109/L, and absolute neutrophil count was 363.7×109/L. Twenty-one percent of patients had a history of thrombotic events, with 13.1% and 8.6% of patients experiencing ≥1 venous or arterial thromboembolic event, respectively. Of the 261 reported thrombotic events, 43.7% occurred after diagnosis of PV. The most common PV symptoms recorded at enrollment (using the Myeloproliferative Neoplasm Symptom Assessment Form) were fatigue (37.1%), pruritus (24.0%), headache (18.6%), insomnia (17.0%), dizziness (13.2%), bone pain (10.5%), and blurred vision (7.9%); 19.7% of 518 evaluable patients had palpable splenomegaly. Fewer than half of patients were receiving aspirin at enrollment (47.7%). The most common PV treatments ± aspirin were phlebotomy (PBT; 63.5%), hydroxyurea (HU; 42.2%), watchful waiting (5.3%), and ruxolitinib (3.1%); 23.0% of patients received PBT + HU. Conclusion: The REVEAL study is unique in that it captures data from both academic and community centers, and therefore includes a broader segment of the PV population typically not described in the literature. REVEAL can provide novel insights into questions related to the contemporary demographics of PV, practice patterns regarding diagnosis and therapy, and the real-world burden of PV and its impact on patients' quality of life and work productivity. Preliminary descriptive data from this early subset of patients suggest that a high proportion of patients report having PV-related symptoms at diagnosis, fewer patients are treated with aspirin than expected, and that thromboembolic event rates remain high after diagnosis. Disclosures Stein: Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees. Moliterno:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Boccia:Incyte Corporation: Honoraria. Naim:Incyte Corporation: Employment, Equity Ownership. Cordaro:Incyte Corporation: Employment, Equity Ownership. Peng:Incyte Corporation: Employment, Equity Ownership. Sun:Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Mesa:Promedior: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; NS Pharma: Research Funding; CTI Biopharma: Research Funding; Gilead: Research Funding; Pfizer: Research Funding; Incyte Corporation: Research Funding; Genentech: Research Funding.

Abstract Background : Polycythemia vera (PV) is a myeloproliferative neoplasm driven by JAK/STAT activation and is associated with erythrocytosis and a broad symptom burden that may negatively impact patient quality of life (QoL). Hydroxyurea (HU) is often used as first-line therapy for high-risk patients but may not effectively control or reduce symptom burden. RESPONSE is a phase III trial comparing ruxolitinib (RUX) with best available therapy (BAT) in patients with PV who were intolerant of or resistant to HU according to modified European LeukemiaNet (ELN) criteria. The primary study endpoint (a composite of hematocrit control and ≥35% spleen volume reduction at Week 32) was achieved by 21% of patients in the RUX arm vs 1% in the BAT arm (P<0.0001); 77% of patients in the RUX arm achieved at least one component of the primary endpoint. The current analysis was conducted to evaluate the effect of RUX on PV-related symptoms and QoL measures in the RESPONSE trial. Methods : Patients with PV aged ≥18 years, resistant to or intolerant of HU (modified ELN criteria) with splenomegaly, and who required phlebotomy for hematocrit control were randomized 1:1 to receive open-label RUX 10 mg twice daily (BID) or BAT (administered based on investigator judgment). Dose adjustments were permitted (RUX, 5-mg BID increments [25 mg BID max]; BAT was adjusted per investigator judgment). Objectives of this analysis included assessment of improvement in symptom burden as assessed by patient-reported outcomes using the 14-item modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF), the Pruritus Symptom Impact Scale (PSIS), the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), and the Patient Global Impression of Change. The 14-item MPN-SAF (graded from 0 [absent] to 10 [worst imaginable]) comprised symptoms related to cytokines (tiredness, itching, muscle ache, night sweats, and sweats while awake), hyperviscosity (vision problems, dizziness, concentration problems, headache, numbness/tingling, ringing in ears, and skin redness), and splenomegaly (abdominal discomfort and early satiety). Changes in total symptom score (TSS; maximum score = 140) and individual symptom scores from baseline to Week 32 were summarized by treatment group. For the EORTC QLQ-C30 Global Health Status/QOL score, the percentage of patients with a minimally important difference (MID) from baseline (10-point change) at Week 32 was summarized. Results : Overall, 222 patients were randomized (RUX, 110; BAT, 112). Median age (range) was similar between arms (RUX, 62.0 [34.0–90.0]; BAT, 60.0 [33.0–84.0]); the RUX and BAT arms were 60% and 71% male, respectively. At Week 32, a higher proportion of patients in the RUX vs the BAT arms had a ≥50% improvement in MPN-SAF TSS (49% vs 5%, respectively) and MPN-SAF symptom cluster scores (cytokine, 64% vs 11%; hyperviscosity, 37% vs 13%; splenomegaly, 62% vs 17%). Median percentage changes in individual symptom scores are presented in the Table. Mean changes from baseline at Week 32 on the 5 items of the PSIS indicated that the severity of pruritus and its interference on daily life improved with RUX (range, −1.5 to −2.2) and was unchanged/worsened with BAT (range, −0.1 to 0.3). Treatment with RUX vs BAT was associated with improved mean changes from baseline at Week 32 on EORTC QLQ-C30 symptom subscales, functional subscales, and Global Health Status/QOL (Table); 46% of RUX patients versus 10% of BAT patients achieved an MID in Global Health Status/QOL (Figure). At Week 32, RUX patients were more likely to rate their global impression of symptom changes as “very much improved” or “much improved” (67%) vs BAT patients (13%). Conclusion : In patients with PV who were resistant to or intolerant of HU, treatment with RUX was associated with greater and clinically meaningful improvements in PV-related symptom burden and QoL measures compared with BAT. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Mesa: Incyte Corporation: Research Funding; CTI: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Eli Lilly: Research Funding; Promedior: Research Funding; NS Pharma: Research Funding; Sanofi: Research Funding; Celgene: Research Funding. Off Label Use: Ruxolitinib is a JAK1/JAK2 inhibitor approved for the treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Verstovsek:Incyte Corporation: Research Funding. Kiladjian:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Masszi:Novartis Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Durrant:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Harrison:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. He:Incyte Corporation: Employment, Equity Ownership. Jones:Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Li:Novartis Pharmaceuticals: Employment, Equity Ownership. Côté:Novartis Pharmaceuticals: Employment, Equity Ownership. Habr:Novartis Pharmaceuticals: Employment, Equity Ownership. Vannucchi:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Abstract Background:Patients with polycythemia vera (PV) often present with a broad range of clinical characteristics that may contribute to increased risks of cardiovascular (CV) morbidity and mortality, including thrombotic events (TE). Limited contemporary real-world data have been reported about the clinical burden of PV and treatment patterns in the United States. The ongoing REVEAL study collects data on disease burden, clinical management, patient-reported outcomes, and healthcare resource utilization for patients with PV in the United States. This analysis reports clinical characteristics, including underlying CV risk factors, for patients enrolled in the REVEAL study as of April 28, 2016. Methods: REVEAL is a multicenter, nonrandomized, prospective, observational study enrolling patients ≥18 years of age with a PV diagnosis who are actively managed in an academic or community setting. For this analysis, data regarding PV disease and diagnosis, clinical characteristics, and treatment patterns were collected at enrollment during usual-care visits and were based on physician assessment, electronic medical records, and local laboratory values. Ten-year CV risk factors selected for this analysis were adapted from the Framingham Heart Study for CV diseases. Results: At data cutoff, 2307 patients were available for this analysis. Mean (SD) age was 66.3 (12.2) years, 54.4% were male, 89.9% were white, 62.7% had at least some college education, and 51.1% were retired. Approximately 6% of patients had a family history of PV, primarily in parents (35.1%) and siblings (33.8%). A history of second malignancies was reported for 344 patients (14.9%). The majority of patients (84.6%) were diagnosed with PV based on an abnormal blood test alone or in combination with a bone marrow test. Among patients who were diagnosed with a mutational test (n=1078), 95.2% were diagnosed via an abnormal JAK2V617F test result. Abnormal hemoglobin (57.3%), hematocrit (55.4%), or both (47.5%) were among the most common blood values assessed for PV diagnosis. At diagnosis, 58.5% of patients were classified with high-risk PV (age ≥60 years or history of a TE); this percentage increased to 77.3% at REVEAL enrollment. The average (SD) disease duration from diagnosis to enrollment was 5.8 (6.1) years. At enrollment, 91.5% of patients were under active management for PV (phlebotomy ± aspirin, 34.0%; hydroxyurea ± aspirin, 27.0%; and phlebotomy + hydroxyurea ± aspirin, 23.2%). Underlying CV risk factors that were either diagnosed or treated in 86.0% of enrolled patients included hypertension (66.5%), history of smoking (46.2%), current smoking at enrollment (10.9%), obesity (34.2%), hyperlipidemia (27.4%), and diabetes (14.8%). At enrollment, 431 (18.7%) patients reported having ≥1 TE, including 181 patients who had a TE between PV diagnosis and enrollment. Venous and arterial TEs were reported in 11.1% and 8.6% of patients, respectively. Most commonly reported venous TEs were deep vein thrombosis (5.9%) and pulmonary embolism (2.5%); most common arterial TEs were cerebrovascular arterial thrombosis including transient ischemic attack (5.1%) and acute myocardial infarction (1.7%). Increased rates of TEs were observed among patients with hyperlipidemia (23.6%) and hypertension (21.0%; Table 1), compared with patients who did not have any risk factors (10.5%). Conclusion: A large proportion of patients in the REVEAL study had 1 or more underlying CV risks, including age, hypertension, smoking, obesity, hyperlipidemia, and diabetes, which may contribute to the risk of thrombosis. Longitudinal data from REVEAL will provide a better understanding of how these factors affect CV outcomes over time. Disclosures Stein: Incyte Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding. Naim:Incyte Corporation: Employment, Equity Ownership. Grunwald:Janssen: Research Funding; Forma Therapeutics: Research Funding; Medtronic: Equity Ownership; Alexion: Membership on an entity's Board of Directors or advisory committees; Ariad: Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Oh:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; CTI: Research Funding. Paranagama:Incyte Corporation: Employment, Equity Ownership. Cordaro:Incyte Corporation: Employment, Equity Ownership. Sun:Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Boccia:Celgene: Consultancy, Honoraria, Speakers Bureau; Amgen/Onyx: Consultancy, Honoraria, Speakers Bureau; Gilead: Speakers Bureau; Genentech: Consultancy, Honoraria, Speakers Bureau; Eisai: Consultancy, Honoraria, Speakers Bureau. Mesa:Ariad: Consultancy; CTI: Research Funding; Gilead: Research Funding; Galena: Consultancy; Novartis: Consultancy; Promedior: Research Funding; Celgene: Research Funding; Incyte Corporation: Research Funding.