Geyer, Holly L.

AbstractThe field of malignant hematology has experienced extraordinary advancements with survival rates doubling for many disorders. As a result, many life-threatening conditions have since evolved into chronic medical ailments. Paralleling these advancements have been increasing rates of complex hematologic pain syndromes, present in up to 60% of patients with malignancy who are receiving active treatment and up to 33% of patients during survivorship. Opioids remain the practice cornerstone to managing malignancy-associated pain. Prevention and management of opioid-related complications have received significant national attention over the past decade, and emerging data suggest that patients with cancer are at equal if not higher risk of opioid-related complications when compared with patients without malignancy. Numerous tools and procedural practice guides are available to help facilitate safe prescribing. The recent development of cancer-specific resources directing algorithmic use of validated pain screening tools, prescription drug monitoring programs, urine drug screens, opioid use disorder risk screening instruments, and controlled substance agreements have further strengthened the framework for safe prescribing. This article, which integrates federal and organizational guidelines with known risk factors for cancer patients, offers a case-based discussion for reviewing safe opioid prescribing practices in the hematology setting.

Objectives: Patients admitted to a medical-surgical unit infrequently require early transfer to higher level care, although how their inpatient length of stay compares to untransferred patients, or those directly admitted to intermediate care, is unknown. We sought to compare the inpatient length of stay of these groups. Design: Single-site retrospective analysis. Setting: An academic hospital specializing in complex care. Patients: We evaluated 23,694 patients admitted to the Hospital Internal Medicine service over a 4-year period (January 1, 2013, to December 31, 2016). Interventions: None. Measurements and Main Results: Using 6- and 24-hour definitions of early transfer, we categorized patients as admitted to medical-surgical unit without early transfer (medical-surgical unit), transferred (TX) early to higher level care, or initially admitted to an intermediate care unit. We report patient characteristics and inpatient length of stay adjusted for patient demographics (age and sex) and initial acuity (measured by Emergency Severity Index). There were significant increases in both unadjusted inpatient length of stay (6 hr: medical-surgical unit = 73.4 hr, TX = 137.9 hr, intermediate care unit = 101.1 hr; 24 hr: medical-surgical unit = 72.4 hr, TX = 141.9 hr, intermediate care unit = 98.2 hr; p < 0.01 for all groups) and adjusted inpatient length of stay (6-hr definition: medical-surgical unit = 50.9 hr [95% CI, 50.3–51.6 hr], TX = 100.4 hr [90.4–112.0 hr], intermediate care unit = 72.3 hr [70.6–74.0 hr]; 24-hr definition: medical-surgical unit = 50.3 hr [49.7–50.9 hr], TX = 108.3 hr [101.5–116.0 hr], intermediate care unit = 70.7 hr [69.0–72.3 hr]; p < 0.0001 for comparison of TX to medical-surgical unit and intermediate care unit in both groups). The increases in inpatient length of stay for the TX groups were not explained by differences in demographics or acuity. Conclusions: In a single facility study, patients admitted to a medical/surgical unit who require early transfer to intermediate care unit have a significant and unexplained increase in inpatient length of stay. This unexplained increased inpatient length of stay suggests that triage to the appropriate inpatient unit significantly affects inpatient length of stay.

Abstract Background: Thrombotic and hemorrhagic complications are commonly encountered in uncontrolled essential thrombocythemia (ET). Both anagrelide and hydroxyurea (HU) have proven efficacious in cytoreduction as well as reducing these events and remain first line therapy for most high-risk ET patients. Independent of their role in risk-reduction, little is known about how these therapies impact patient symptomatology or quality of life. In this study, we compared the clinical and symptomatic profiles of ET patients receiving HU or anagrelide against patients with no previous experience with these agents. Methods: Data was assessed from a prospectively collected international database of ET patients in which demographics, disease features, and ET symptoms utilizing the myeloproliferative neoplasm symptom assessment form (MPN-SAF; Scherber et al, 2011). The MPN-SAF includes the patient's perceptions of common MPN-related symptoms and overall quality of life (QOL) on a 0 (absent) to 10 (worst imaginable) scale. Total symptom score (TSS) was computed based on symptom items using the published scoring algorithm on a 0 (all reported symptoms absent) to 100 (all reported symptoms worst imaginable) scale. ET risk scores were calculated using the IPSET scoring algorithm (Passamonti 2012). Thrombocytopenia was defined as a platelet count <100 x 10(9)/L, anemia was defined as hemoglobin<10 g/dL and leukopenia was defined as a white blood cell count <4.0 x 10(9)/L. Associations between the MPN-SAF individual symptoms were investigated using chi-square test for categorical data and ANOVA F-test for continuous variables. Results Hydroxyurea vs. HU Naive A total of 402 ET patients with active HU use were compared to 392 ET patients with no history of HU use. Patients using HU were older (63.5 years vs. 52.3 years, p<0.001) and had a greater concentration of both high risk (24.9% vs. 11.4%, p=0.001) and intermediate risk (53.9% vs 38.4%, p<0.001) patients. They also had a higher rate of prior thrombosis (29.8% vs 11.3%, p<0.001) and leukopenia (10.1% vs. 3.0%, p<0.001). No differences were noted between gender, a history of prior hemorrhage, red blood cell transfusion requirements, or the presence of anemia/thrombocytopenia. In comparing symptom profiles, no significant differences were noted between TSS or individual symptoms with the exception of slightly more severe cough in HU patients (1.5 vs. 1.1, p=0.02, Figure 1). Anagrelide vs. Anagrelide Naive A total of 49 ET patients with active anagrelide use were compared to 794 ET patients with no history of anagrelide use. Patients using anagrelide had a longer mean disease duration (8.1 years vs. 5.8 years) and were more anemic (9.1% vs. 1.2%, p<0.001). No differences were noted between age, gender, risk scores, the presence of leukopenia/thrombocytopenia, a history of prior thrombosis or hemorrhage complications or red blood cell transfusion requirements. Additionally, there were no significant differences between TSS or individual symptom items (Figure 1). HU vs. Anagrelide A total of 402 patients currently using HU were compared to 39 patients currently using anagrelide. Overall, HU users were slightly older (63.5 years vs. 55.1 years, p<0.001) with a greater population of patients meeting high risk criteria (24.9% vs. 2.8%, p=0.002) and having a history of prior thrombosis (29.8% vs. 12.8%, p=0.02). Patients receiving anagrelide had a slightly longer disease duration (8.2 years vs. 6.0 years, p=0.0446). In comparing symptom profiles, no differences were noted in TSS or individual symptom items between cohorts. Discussion In this retrospective analysis, it does not appear cytoreduction with either HU and/or anagrelide has a significant impact on ET symptom burden despite reducing vascular events. Importantly, the higher risk scores in HU patients did not translate directly into greater patient symptomatology supporting previous studies demonstrating a poor association between these two items. Prospective trials measuring ET symptom change, in the setting of randomized trials will better quantify impact of cytoreduction on symptom burden as well as quantify impact of newer agents such as interferon or jak inhibition. Figure 1. Symptom Comparisons Between HU, Anagrelide and Other Therapy Figure 1. Symptom Comparisons Between HU, Anagrelide and Other Therapy Disclosures Kiladjian: Incyte Corporation: Consultancy; Novartis: Other: Travel grant; Research Funding paid to institution (Hôpital Saint-Louis et Université Paris Diderot); Novartis: Consultancy. Zweegman:Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Harrison:Sanofi: Honoraria, Speakers Bureau; Shire: Speakers Bureau; Gilead: Honoraria; CTI Biopharma: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau. Cervantes:Sanofi-Aventis: Consultancy; Novartis: Consultancy, Speakers Bureau; CTI-Baxter: Consultancy, Speakers Bureau. Barbui:Novartis: Speakers Bureau. Etienne:ARIAD: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: Congress Travel/Accomodations, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau. Roy:Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding. te Boekhorst:Novartis: Consultancy; CTI Biopharma: Consultancy. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Speakers Bureau; Novartis: Other: Research Funding paid to institution (University of Florence), Research Funding; Baxalta: Membership on an entity's Board of Directors or advisory committees. Mesa:Novartis. Research- incyte, Gilead, cti, Genentech, promedior, NS Pharma: Consultancy.

Abstract Introduction Individuals with the Philadelphia chromosome negative myeloproliferative neoplasms (MPNs) have previously been shown to experience symptoms in excess to age and comorbidity matched peers. Although numerous assessments of symptom burden and quality of life have been utilized among MPN populations, including the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), Patient Reported Outcomes Measurement Information System (PROMIS¨) fatigue scale, and Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) and the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-10), there are currently no validated assessments of overall health. Developed by the EuroQol Group to assess heath status, the EQ-5D is an internationally validated self-assessment which may be useful in the assessment of health state among MPN patients (Annals of Medicine, 2001. 33:337-43). Methods The EQ-5D evaluates five dimensions of mobility, self-care, usual activities, pain/discomfort and anxiety/depression, on a scale from no problems to extreme problems and assesses patient reported health state via a numerical visual analogue scale (VAS) ranging from 0 to 100. The health state score is a composite score of these items ranging from 0 to 1.0, with higher scores indicating an improved health state. EQ-5D survey participants were essential thrombocythemia (ET) and polycythemia (PV) patients participating in the MAJIC United Kingdom (UK) trial. The MAJIC trial is a randomized, phase II study of best available therapy versus JAK inhibition in individuals with PV or ET who have been resistant or intolerant of cytoreduction with hydroxyurea /hydroxycarbamide. This study was one of the first Trials Acceleration Programme (TAP) trials and is funded by Leukaemia Lymphoma Research, with drug supplied by Novartis. Only baseline EQ-5D assessments taken at study enrollment were included in this analysis. Comparative analysis was preformed using the MPN-10 (J Clin Oncol.2012. 30:4098-103). Results: Participant Demographics: Sixty six patients with ET and 55 patients with PV completed the EQ-5D questionnaire. Median respondent age was 65 years old and half of respondents were female (54%). Average MPN duration was 10 years for ET and 9.2 years for PV. EQ-5D Scoring: Severe to extreme difficulties in the items of mobility, self-care, usual activities, pain/discomfort and anxiety/depression were common (Table 1).Patients with PV tended to have higher proportion of patients with severe to extreme difficulties in individual disease dimensions, higher VAS score, and worsened health state compared to their essential thrombocythemia counterparts, although these effects were not significant. Average VAS health score was 70.4 (+21.2) for ET and 66.5 (+19.6). When evaluating the health state composite score, the mean ET score was 0.74 (+0.32) and mean PV score was 0.66 (+0.28). EQ-5D Validation: The EQ-5D had excellent internal consistency (CronbachÕs alpha=0.87) and strong internal correlation. When evaluating external validity, strong correlations existed between the EQ-5D and the MPN-SAF TSS scales for dimensions of mobility, usual activities, pain and overall health state (many items with r >0.5 and p<0.001). Conclusions: The EQ-5D is a valid and accurate instrument for the brief assessment of health state among MPN patients. This instrument demonstrates excellent clinical utility in a large clinical study cohort and can be used in both clinical practice and trial settings. When comparing EQ-5D health state scores, ET and PV patients had worsened health than the general UK population age 60 to 69 (0.774; Med Decis Making. 2011.31(6)800-4), but similar health to individuals with other malignancies including breast cancer (0.760), prostate cancer (0.743), and lung cancer (0.689). Disclosures Mesa: NS Pharma: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Incyte Corporation: Research Funding; Pfizer: Research Funding; Promedior: Research Funding; CTI Biopharma: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Pfizer: Research Funding. Harrison:CTI Biopharma: Consultancy, Honoraria, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau; Shire: Speakers Bureau; Gilead: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau.

Background: Quality of life (QOL) is predictive of survival in many malignancy types, including myeloproliferative neoplasms (MPNs; Scherber 2017, Sloan 2012, Montazeri 2009, Nilsson 2017). We have previously characterized that an association exists between symptom burden and QOL among MPN patients, but due to the disease specificity of symptoms, symptoms rather than QOL remains a key therapeutic endpoint (Scherber 2017, NCCN Guidelines). Despite these advancements, our understanding of the extent that different patient and disease characteristics, including symptoms, contribute to overall QOL has remained elusive. In this analysis, we utilized information from a large survey of MPN patients to develop a model of QOL that establishes the degree that individual variables contribute to QOL, including psychosocial variables, comorbidities, and MPN disease symptoms. Methods: The FATIGUE survey of MPN patients (Scherber 2016) investigated self-reported symptoms using the MPN10 (Scherber 2012), depression utilizing the Profile of Mood States-Brief (POMS-B, McNair 1971), Patient Health Questionnaire (PHQ-2, Kroenke 2003) and Mental Health Inventory (MHI-5, Berwick 1991), and QOL utilizing a single numeric analog scale (range 0-10) regarding overall quality of life. Linear regression analysis was utilized to establish the relationship between individual symptoms and QOL, and a structural equation model (SEM) was used to identify complex relationships among patient demographics, behavioral factors, comorbidities, and QOL. Results: A total of 914 patients from the online survey lived in the USA and provided data for this analysis. Average age was 62 with 67% of patients being female and the mean BMI was 25. Education varied across middle school or high school education (22%), undergraduate or college degree (44%), masters (26%), to doctorate (8%). 43% of respondents were employed. Fatigue (β coefficient 0.23, p<0.001), inactivity (β 0.21, p<0.001), concentration difficulties (β 0.13, p<0.001), sad mood (β 0.18, p<0.001), and night sweats (β 0.05, p=0.03) showed statistically significant impact on QOL. SEM Model: We developed the SEM model in Figure 1. Out of all variables analyzed, MPN total symptom burden demonstrated the strongest association with (β 0.89) with QOL, followed by depression (β 0.76). Comorbidities, including COPD and renal issues, age, and body mass index abnormalities had some impact on symptoms (all β <0.40), but did not demonstrate a significant impact on QOL. Comparative Fit Index (CFI) was 0.905 and root mean square error of approximation (RMSEA) was 0.051 (0.048, 0.054) indicating good fit. Conclusions: Previous clinical trials of JAK inhibition have targeted improvement in symptoms as a key endpoint, and ultimately demonstrated improvements in overall survival. The mechanism of this survival benefit has not been fully explored. This analysis suggests that symptoms and mood are strongly associated and potentially a major contributor to QOL among MPN patients, whereas other major comorbidities and age are not as strongly correlated. Efforts are underway to analyze more comprehensive datasets to better understand the role of other variables, including marriage status and financial concerns, on QOL. Disclosures Scherber: Blueprint: Other: Ad board; Incyte: Consultancy; Gilead: Consultancy. Hasselbalch:Novartis: Research Funding; AOP Orphan Pharmaceuticals: Other: Data monitoring board. Mesa:Baxalta: Consultancy; LaJolla: Consultancy; Genentech: Consultancy; Celgene Corporation: Research Funding; Samus: Research Funding; AbbVie: Research Funding; NS Pharma: Research Funding; Novartis: Consultancy, Honoraria, Other: travel, accommodations, expenses; CTI: Research Funding; Galena Biopharma: Consultancy; Pfizer: Research Funding; Incyte: Other: travel, accommodations, expenses, Research Funding; Genotech: Research Funding; AOP Orphan Pharmaceuticals: Honoraria, Other: travel, accommodations, expenses; PharmaEssentia: Research Funding; Gilead Sciences: Research Funding; Promedior: Research Funding; Shire: Honoraria; Sierra Oncology: Consultancy.

Abstract Introduction: Myeloproliferative Neoplasm (MPN) patients encounter debilitating pain syndromes as a result of their disorder. Opioids are frequently employed in cancer-related pain but have been increasingly recognized for their risk profiles including accidental overdose, addiction and death. With many MPN patients facing near-normal life expectancies, chronicity of opioid use may increase the risk of adverse events. In this survey, we evaluated the prevalence of MPN opioid use, risk factors for negative outcomes and compared the features of this population to MPN patients not receiving opioid therapy. Methods: This study was performed by the MPN Quality of Life Study Group. A survey was designed by a team of MPN investigators experienced with MPN symptomatology. Patients completed the MPN-10, a 10 item survey of MPN symptoms completed on a 0 (absent) to 10 (worst imaginable) scale (Blood. 2011 Jul 14;118(2):401-8). Other surveyed tools included the Opioid Risk Tool (ORT) as well as DSMV criteria for Opioid Use Disorder (OUD). The survey was posted on high-traffic MPN-related webpages focused on patient education and advocacy (MPN Forum, MPN Net, MPN Research Foundation, MPN Voice)for a total of 28 days. Patients currently receiving opioids were compared to patients not receiving opioids and statistical significance was defined as p<0.05. Results Demographics A total of 416 patients completed the survey and were compared by active opioids use (n=69) vs. no active opioid use (n=347). Patients described a history of myelofibrosis (MF, 28.8%), polycythemia vera (PV, 44.2%) and essential thrombocythemia (ET, 26.9%). Most MPNs were diagnosed between 1-3 years ago (22.2%), 3-10 years ago (35.0%) or >10 years ago (30.4%). Patients were furthermore of expected mean age (60.7), primarily female (75.0%) and from the United States (66.6%). Few patients had a history of transformation to acute leukemia (0.5%), severe bleeding (12.3%) or blood clot (26.5%). Mean individual symptom scores and prevalences were 3.0 and 65.6% for abdominal discomfort and 3.3 and 59.4% for bone pain, respectively, indicating a low to moderate symptom burden. Patients Receiving Opioid Therapy Patients on opioid therapy (n=69) displayed a number of high risk features for adverse outcomes including a personal history of substance abuse (20.2%), respiratory disease (33%) and mental health disorders (60.1%). By DSMV criteria, 5.9% of opioid patients scored 'mild' and 2.9% scored 'moderate' for OUD (total 8.8%), consistent with prevalence in the general population. Approximately 24.6% of opioid-using patients scored moderate to high risk on the ORT but despite this, did not appear more likely to meet criteria for OUD (p=0.81). Palliative care and pain management were involved in only 34.3% of patients and side effects of opioids were discussed in only 70.1% of all cases. Opioid vs. Non-Opioid Patients Compared to patients not receiving opioid therapy, patients currently on opioid treatment were more likely to describe more frequent and/or more severe abdominal discomfort (88.4% vs. 61.0%, p<0.001; mean 5.0 vs. 2.6, p<0.001), bone pain (87.0% vs. 53.9%, p<0.001; mean 5.6 vs. 2.4, p<0.001), unintentional weight loss (41.2% vs. 21.4%, p=0.001), inactivity (94.2% vs. 71.5%, p<0.001), early satiety (84.1% vs. 58.2%, p<0.001), and impaired quality of life (mean 4.9 vs. 6.6, p<0.001). They were also more likely to describe regularly taking pain medications (85.5% vs. 34.5%, p<0.001) as well as attempt non-pharmacological treatments to manage symptoms (Figure 1). Despite more aggressive pain treatment approaches, only 42% of opioid patients reported satisfaction with their current pain plan vs. 62.2% of patients not receiving opioid therapy. Conclusions: MPN patients face significant symptom burden despite often limited reduction in life expectancy. Patients furthermore demonstrate a high prevalence of risk factors for opioid-related complications including overdose and substance misuse. Despite aggressive pain regimens, opioid patients are less likely to voice adequate symptom control or satisfaction with their pain treatment plans. Providers should be cognizant of opioid-related complications and consider subspecialty pain management referrals or adaptation of the JCO Clinical Practice Guidelines for Management of Chronic Pain in Survivors of Adult Cancers (J Clin Oncol. 2016 Sep 20;34(27):3325-45). Disclosures Scherber: Orphan Pharmaceuticals: Honoraria; Incyte: Consultancy. Palmer:Novartis: Research Funding. Dueck:Phytogine: Employment; Pfizer: Honoraria; Bayer: Employment. Mesa:Gilead: Research Funding; Novartis: Consultancy; CTI: Research Funding; Galena: Consultancy; Incyte: Research Funding; Promedior: Research Funding; Ariad: Consultancy; Celgene: Research Funding.

Abstract Introduction: MPN-related pain, including abdominal discomfort (53.2%), and bone pain (48.5%), is a prevalent complaint within the disorder and is associated with impaired patient quality of life, reduction in most functional domains and overall poor prognosis. Non-targeted treatments for MPN disorders have been previously shown to provide little symptomatic relief for MPN pain. To date, little is known about patient viewpoints on MPN pain, its relationship to other chronic pain syndromes and the impact of pharmacologic and non-pharmacologic pain therapies. In this study, we performed an international survey of MPN patients to better understand the prevalence and management of MPN pain. Methods: This study was performed by the MPN Quality of Life Study Group. A survey was designed by a team of MPN investigators experienced with MPN symptomatology. Survey content included the Barriers Questionnaire II (BQII), a 27-item survey validated to assess patient belief barriers to optimal management of cancer pain measured on a 0 (do not agree at all) to 5 (agree very much) scale (Pain. 2002 Oct;99(3):385-96.). Patients also completed the MPN-10, a 10-item survey of MPN symptoms completed on a 0 (absent) to 10 (worst imaginable) scale (Blood. 2011 Jul 14;118(2):401-8). The survey was posted on high-traffic MPN-related webpages focused on patient education and advocacy (MPN Forum, MPN Net, MPN Research Foundation, MPN Voice) for a total of 28 days. Survey questions evaluated patient demographics, pain histories, current and prior treatment strategies, as well as satisfaction with and barriers to available treatment options. Results: Demographics A total of 502 MPN patients (MF 26.9%, PV 44.2%, ET 28.9%) completed the survey. Patients were of expected mean age (60.5 years) and primarily female (74.9%). Most were from the United States (66.7%) and primarily English speaking (92.2%). Patients described being diagnosed with their MPN 3 to 10 years (35.4%) or >10 years ago (30.8%). Splenic enlargement was vocalized by 36.5% of patients and few patients had had a known history of blood clots (25.4%), severe bleeding (13.3%), conversion to acute leukemia (0.4%) or prior bone marrow transplant (1.4%). Patients described a treatment history of a variety of MPN therapies including aspirin (82.7%), hydroxyurea (60.6%), phlebotomy (40.6%), ruxolitinib (25.9%), interferon (18.5%), anagrelide (17.3%), active clinical trial (5.0%) and radiation treatment (0.4%). Pain Severity, Prevalence and Treatments Among surveyed patients, the MPN-10 mean was 28.3. Mean individual symptom scores and prevalence were 3.1 and 65.6% for abdominal discomfort and 3.0 and 60.4% for bone pain, respectively indicating a low to moderate symptom burden. Most patients had no prior history of chronic pain prior to their MPN diagnosis (47.1%), with chronic abdominal pain and chronic bone/muscle pain noted prior to MPN development in 5.6% and 20.8% of patients, respectively. Most patients felt that their chronic pain has either stayed the same (26.2%), worsened (28.3%) or significantly worsened (14.5%) since their MPN diagnosis. Many patients found pharmacologic and non-pharmacological therapies efficacious for individual pain symptoms, and 42.1% described regularly taking medication to control their pain (Table 1). Barriers to Pain Management Overall, 42.3% of MPN patients reported being unsatisfied with their current pain management plan. Despite this, only 43.5% of patients stated that their MPN providers discussed pain during office visits. Palliative Care (3.1%) and Pain Management (7.3%) were infrequently engaged. On the BQII, patients described being confident that cancer can cause pain (mean 4.2, SD 1.1) but did not necessarily expect to have pain following their MPN diagnosis (mean 2.2, SD 1.8). Conclusion Chronic pain (abdominal, bone) is a prevalent and undermanaged feature of MPN disorders. Chronic non-MPN pain is further complicated by the development of the disorder. Many MPN patients lack understanding on its prevalence and furthermore feel ill-equipped to manage it. Patients have, however, found symptomatic benefit from various pharmacological and non-pharmacological treatment modalities that require further exploration. Results from this study suggest MPN patients should be assessed regularly for pain and offered early referral to specialized services for evaluation, source identification and treatment. Table 1. Table 1. Disclosures Scherber: Incyte: Consultancy; Orphan Pharmaceuticals: Honoraria. Mesa:Ariad: Consultancy; Galena: Consultancy; CTI: Research Funding; Incyte: Research Funding; Promedior: Research Funding; Gilead: Research Funding; Novartis: Consultancy; Celgene: Research Funding. Dueck:Bayer: Employment; Pfizer: Honoraria; Phytogine: Employment. Palmer:Novartis: Research Funding.

Abstract Background: Myeloproliferative neoplasms (MPN) including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) are clonal hemopathies characterized by burdensome symptom profiles and impaired quality of life. Treatments include pharmacologic approaches, phlebotomy, and bone marrow transplant. Outcome studies have historically focused on hematologic improvement and survival benefit. Few prospective studies have evaluated patient-reported symptoms and quality of life outcomes after standard therapy. The Myeloproliferative Neoplasm Quality of Life (MPN-QOL) Study Group aims to objectively quantify symptomatic response to standard treatments. Here we provide updated results for the prospective MPN Experimental Assessment of Symptoms by Utilizing Repetitive Evaluation (MEASURE) trial. Methods: The MEASURE trial is a prospective international cohort study evaluating responsiveness of the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS or MPN-10) in an anticipated 480 ET, PV, and MF patients receiving non-experimental medical therapy and/or phlebotomy. Patients complete the MPN-SAF TSS (JCO 2012) for seven consecutive days at enrollment then again for seven days between 90 days and six months later. Patients also complete the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) and M.D. Anderson Symptom Inventory (MDASI) instruments at enrollment and on the first day of the second assessment. Physicians report demographic, laboratory, and clinical data. Results: Demographics To date, 340 patients have enrolled and 270 have completed both study visits. Participants include ET (60%), PV (29%), and MF (12%; including 68% primary MF, 12% post-ET, 20% post-PV) patients. Enrolled patients are 51% male. The most common therapies received prior to enrollment were aspirin (34%), phlebotomy (15%), hydroxyurea (14%), and warfarin/clopidogrel/anticoagulation (6%). The most common current MPN therapies were hydroxyurea (67%), aspirin (24%), phlebotomy (9%), and ruxolitinib (8%). Information on mutational analysis was also collected; 77% of patients have a known JAK2 V617F mutation, 3% have an MPL W515 mutation. Symptom Measures On the MPN-SAF TSS, the majority of individual symptoms assessed did not change significantly between the two assessment time points while on standard therapy. Notable exceptions were a significant decrease in weight loss (mean 2.0 vs. 1.7 on a 0=absent to 10=worst imaginable scale, p=0.005) and a significant worsening in quality of life (mean 3.6 vs. 3.8 on a 0=as good as it can be to 10=as bad as it can be scale, p=0.04). No changes were seen in other symptoms including early satiety, abdominal discomfort, night sweats, fatigue, inactivity, poor concentration, bone pain, itching, or fever. Similarly, the cumulative MPN-SAF TSS score remained stable at a mean of 24.4 over the treatment period. These findings were congruent with those observed using the EORTC QLQ-C30 instrument, with no significant changes seen in emotional, physical, role, cognitive, or social functioning. Finally, the MDASI also revealed a lack of change in either symptom severity (mean 2.7) or symptom distress (mean 3.0) scores, which remained stable over the study period. Discussion: Myeloproliferative neoplasms are associated with burdensome symptoms that significantly compromise quality of life. To date, no studies have quantified symptomatic response to standard-of-care treatments. Overall, results from the MEASURE study suggest that standard treatments have limited systematic impact on patient symptomatology over time, with no improvements in overall quality of life. However, we note the relatively low proportion of patients in this cohort treated with ruxolitinib, which has been shown previously to improve symptom burden, and this may have impacted the symptom responses seen in the group as whole; detailed responses by treatment and MPN subtype will be presented. Figure. Figure. Disclosures Dueck: Pfizer: Honoraria; Bayer: Employment; Phytogine: Employment. Ross:BMS: Honoraria; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Research Funding. Tam:Janssen: Honoraria, Research Funding; Gilead: Honoraria; AbbVie: Honoraria, Research Funding; Pharmacyclics: Honoraria, Travel funding; AbbVie: Honoraria, Research Funding; Roche: Honoraria; Beigene: Honoraria, Other: Travel funding; Pharmacyclics: Honoraria; Gilead: Honoraria; Roche: Honoraria; Beigene: Honoraria, Other: Travel funding. Radia:Novartis: Speakers Bureau; Blueprint: Consultancy. Mesa:UT Health San Antonio - Mays Cancer Center: Employment; Celgene: Research Funding; NS Pharma: Research Funding; Pfizer: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Promedior: Research Funding; CTI Biopharma: Research Funding; Incyte Corporation: Research Funding; Novartis: Consultancy.

Abstract Introduction Patients with myeloproliferative neoplasms (MPN) typically experience debilitating symptom profiles and profound quality of life (QoL) decrements. Characterizing symptom burden in MPN clinical trials is vital to inform efficacy analyses. Previous studies have shown clinicians and researchers depend on patient-reported outcomes (PROs) to glean disease-related symptoms and signs of QoL decline. The current literature also shows that integrating PROs into the routine care of patients with cancer is associated with increased survival compared with usual care. However, the extent to which PROs are employed in MPN clinical trials is undescribed. ClincalTrials.gov is a registry of clinical trials mandated by the US Congress and implemented in 2000 by the National Institutes of Health. This study used data from ClinicalTrials.gov to evaluate the characteristics of MPN clinical trials over time and their use of PROs as primary and secondary outcomes. Methods The statistical software R and the rclinicaltrials package were used to download data from ClinicalTrials.gov. Trial data were included in this study if the following criteria were met: (1) the words essential thrombocythemia, polycythemia vera, myelofibrosis, or myeloproliferativeneoplasm (MPN) were used in the registered primary disease condition or official trial title; (2) the trial start date was between January 1, 2000 - July 1, 2018; (3) primary/secondary outcome data were available. Trial outcome data were then parsed for PRO text phrases including MPN-Symptom Assessment Form, quality of life, questionnaire, patient-reportedoutcome, and more specific PRO items (e.g., bone pain, concentration problems, and depression). Descriptive statistics and regression analysis were used to assess rates of primary/secondary outcomes over time. Results Clinical trial characteristics There were 535 trials satisfying the inclusion criteria. Since 2000, the number of registered MPN-related clinical trials ranged from 11 to 36 trials per year with 28 trials registered annually on average (Figure 1). Of the 535 trials, 470 (88%) were interventional and 65 (12%) observational. Trials often employed multiple intervention types including: drug (77%); procedure (28%); biological (19%); radiation (13%); genetic (3%); behavioral (2%); device (2%); dietary supplement (1%); other (24%) [percentages do not sum to 100% as categories are not mutually exclusive]. Eligibility criteria varied widely, though most used 18 years old as the minimum age requirement (71%; 379/535) and nearly all included both genders (>99%; 533/535). PRO outcomes over time Of the 535 MPN trials, the number of primary outcomes within MPN trials did not change over time (p=.50) with an average of 1.6 per trial. Around 8% of MPN clinical trials had PRO-related primary outcomes; this rate also did not change over time (Figure 1: solid red line; p=.97). However, the total number of secondary outcomes per trial has increased since 2000 (p<.001). From 2000-2005, 2006-2011, and 2012-2018 there was an average of 2.8, 3.3, and 5.2 secondary outcomes per trial, respectively. Also, the proportion of MPN clinical trials with PRO-related secondary outcomes has increased steadily over time (Figure 1: dashed blue line; p<.001). On average, from 2000-2005, 2006-2011, and 2012-2018 the proportion of MPN clinical trials with PRO-related secondary outcomes increased from 8% to 23%, to 33%. Conclusion Analysis of ClinicalTrials.gov data suggest that patient-reported outcomes are being implemented into MPN clinical trials at increasing rates. While this suggests that MPN trials are becoming more patient-centered, PROs are included more often as secondary endpoints than primary endpoints. This analysis also suggests an increase in the number of secondary endpoints in recent years in MPN clinical trials, consistent with observed trends of growing complexity and increasing amount of data captured in clinical trials in general. Disclosures Mesa: Ariad: Consultancy; Galena: Consultancy; Gilead: Research Funding; Promedior: Research Funding; Incyte: Research Funding; Novartis: Consultancy; CTI: Research Funding; Celgene: Research Funding. Scherber:Orphan Pharmaceuticals: Honoraria; Incyte: Consultancy. Dueck:Bayer: Employment; Phytogine: Employment; Pfizer: Honoraria.

Abstract Background: Myelofibrosis (MF) is a bone marrow disorder characterized by anemia, splenomegaly and constitutional symptoms. There has been substantial work documenting quality of life (QoL) in patients with MF, however, very little data about patients following allogeneic stem cell transplant (alloSCT) for MF. Many patients decline alloSCT due to concerns secondary to QoL. Methods: Medical facts and patient reported outcomes (PRO) measures were collected within a month prior to transplant, at day 30, 100 and 1 year post alloSCT. PRO measures include Brief Fatigue Inventory, Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), global assessment of change and the Myeloproliferative Neoplasms Symptom Assessment Form (MPN-SAF). The group was measured as a whole, and the patients in the upper quartile of MPN-TSS (the aggregate score of the 10 core items of the MPN-SAF) were also considered. Results: Fifty patients were enrolled on this study, 47 who proceeded with transplant. The median age of the patients was 63, ranging from 35-74. The majority of the patients were male (29, 66%), and Caucasian (43 (96%)). Most patients had primary MF (26, 59%), 9 patients had post-PV MF, and 9 patients had post-ET MF. Twenty patients had DIPSS Intermediate 2 risk disease, and 16 had DIPSS high risk disease. Twenty-six (51%) had a matched unrelated donor, 12 (30%) had a matched related donor and 5 (12%) had a mismatched unrelated donor. The majority of the patients had RIC regimens (35, 88%). At baseline the mean MPN-TSS was 27.7 (out of possible 100), and at day 30, day 100 and 1 year it was 24.6, 32.0, and 25.0, which reflected no significant change between the time points. Interestingly, all the MPN specific symptoms (including fevers, night sweats, pruritis, abdominal pain) had a significant improvement at least one time point following alloSCT. Patients in the highest quartile based on baseline TSS score (12 patients with scores at baseline greater than or equal to 37), had significant improvement in TSS score at day 100, headache at day 30, insomnia at day 100, night sweats at day 100, itching at day 100 and overall QOL at day 100. With regards to the FACT BMT, as would be expected, there was a significant decline in the FACT BMT total score, as well as trial outcome index (TOI) at day 30, but a return to close to baseline by one year. In the global assessment of change, on day 30, 11 (27.5%) of patients reported feeling a little/moderately/very much better overall quality of life since their transplant and 27 (67.5%) felt a little/moderately/very much worse quality of life. At day 100, 11 (31.4%) reported better quality of life and 20 (57%) reported worsening since transplant. By one year, 17 (60.7%) reported feeling better and 7 (25%) reported worsening. These findings did not appear to have a correlation with presence or absence of graft versus host disease. We were unable to assess the impact of conditioning as the majority of the patients had RIC conditioning. Discussion/ Conclusions: Our study evaluated the quality of life in patients with myelofibrosis who have undergone bone marrow transplantation. We have shown that there is very little change in symptom burden over the first year following transplant in general; however, significant improvement was observed in MF specific symptoms, and in patients who had a high symptom burden at baseline. By one year 61% felt that their QoL was better than it was prior to transplant. Our findings suggest that many of the patients do not experience a significant decline in QoL at 1 year after alloSCT, and actually report that their QoL improves. Further investigation is required to validate these findings. Figure. Figure. Disclosures Palmer: Novartis: Research Funding. Dueck:Phytogine: Employment; Pfizer: Honoraria; Bayer: Employment. Mesa:Novartis: Consultancy; NS Pharma: Research Funding; Incyte Corporation: Research Funding; UT Health San Antonio - Mays Cancer Center: Employment; Pfizer: Research Funding; CTI Biopharma: Research Funding; Celgene: Research Funding; Promedior: Research Funding; Gilead: Research Funding; Genentech: Research Funding.