Mazza, Gina L.

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 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: Smoking increases the risk of Philadelphia-chromosome negative myeloproliferative neoplasm (MPN) development as well as increases the risk of thrombotic complications, the major cause of mortality in this population (Blood 2017 130:4199). Guidelines suggest that management of more indolent forms of MPNs include the assessment and mitigation of cardiovascular risk, which includes the management of smoking-related risks (NCCN Guidelines. 2017). In this analysis we sought to examine smoking outcomes and opinions from the perspective of the MPN patient, with the goal of helping to guide MPN patient care. Methods: The internet-based survey was developed by a team of MPN investigators and administered via Mayo Clinic's REDCap. Online recruitment was facilitated via multiple MPN-related webpages including the MPN Forum, MPN Net, MPN Research Foundation, and MPN Voice during June of 2018. Surveyed data included disease demographics such as thrombosis, medications, and smoking history. MPN-specific symptoms were assessed utilizing the MPN-10 (Blood. 2011 Jul 14;118(2):401-8). Data: Participant Demographics: Of the 607 patients who clicked the survey link, 435 patients were eligible for the survey and completed the questions regarding smoking history. Of these, 254 (58%) reported no history of tobacco use, 161 (37%) reported being ex-tobacco users, and 20 (5%) reported being current users. Among those who reported current tobacco use, 50% used premade cigarettes, 27% used self-rolled cigarettes, 20% reported vaping, and 3% reported chewing tobacco or snuff use. Respondents were most often from the US (67%), Australia (12%), the UK (6%) or Canada (6%). The distribution of respondents included 28% with myelofibrosis, 44% with polycythemia vera and 27% with essential thrombocythemia. Over one quarter (26%) of patients had experienced a prior thrombosis, with the most frequent thrombosis types being DVT (9%), stroke or transient ischemic attack (8%), abdominal vein thrombosis (5%), myocardial infarction (2%) and cerebral vein thrombosis (2%). When comparing current/former smokers to never smokers, no significant difference in thrombotic frequency was observed. Smoking Correlates: When evaluating MPN symptoms, current/former smokers reported higher severity of fatigue (mean 5.6 vs 5.0, p=0.02) and inactivity (mean 4.0 vs 3.1, p=0.03) compared to nonsmokers. Additionally, current/former smokers were more likely to experience early satiety (69% vs 58%, p=0.03), inactivity (80% vs 71%, p=0.04), concentration difficulties (82% vs 73%, p=0.04), and reduced quality of life (mean 6.1 vs 6.5, p=0.03) compared to nonsmokers. Although not significant, a trend of higher symptomatology was observed for former/current smokers compared to nonsmokers (MPN-10 total symptom score [TSS] mean 30.4 vs 27.0, p=0.07). Former/current smokers were also more likely than nonsmokers to report heavy alcohol consumption (>7 drinks per week in 9.6% vs 4.0%, p=0.03) and using opioids for pain management (24% vs 11%, p=0.001). Smoking Opinions and Care: As shown in Table 1, less than half of current/former smokers (43%) reported having their physician discuss tobacco use with them. Less than 40% of MPN current or previous smokers were aware of the risk of MPN development due to smoking, although the majority (83%) were aware of the increased thrombotic risk. Less than one quarter (43/181) of current/former smokers reported having utilized pharmacologic therapy to aid cessation. Conclusions MPN patients with current or previous tobacco use demonstrate significantly higher symptom burden than non-smoking counterparts. In terms of patient care, less than half of patients who are current or previous smokers recall having a physician discuss their smoking habits with them. These results highlight the need for enhanced MPN patient counseling by health care providers, both regarding the risks of smoking and available methods to aid cessation. Disclosures Scherber: Orphan Pharmaceuticals: Honoraria; Incyte: Consultancy. Dueck:Phytogine: Employment; Pfizer: Honoraria; Bayer: Employment. Palmer:Novartis: Research Funding. Mesa:Incyte: Research Funding; Galena: Consultancy; Gilead: Research Funding; Ariad: Consultancy; Celgene: Research Funding; Novartis: Consultancy; CTI: Research Funding; Promedior: Research Funding.

The ability to regulate behavior in service of long-term goals is a widely studied psychological construct known as self-regulation. This wide interest is in part due to the putative relations between self-regulation and a range of real-world behaviors. Self-regulation is generally viewed as a trait, and individual differences are quantified using a diverse set of measures, including self-report surveys and behavioral tasks. Accurate characterization of individual differences requires measurement reliability, a property frequently characterized in self-report surveys, but rarely assessed in behavioral tasks. We remedy this gap by ( i ) providing a comprehensive literature review on an extensive set of self-regulation measures and ( ii ) empirically evaluating test–retest reliability of this battery in a new sample. We find that dependent variables (DVs) from self-report surveys of self-regulation have high test–retest reliability, while DVs derived from behavioral tasks do not. This holds both in the literature and in our sample, although the test–retest reliability estimates in the literature are highly variable. We confirm that this is due to differences in between-subject variability. We also compare different types of task DVs (e.g., model parameters vs. raw response times) in their suitability as individual difference DVs, finding that certain model parameters are as stable as raw DVs. Our results provide greater psychometric footing for the study of self-regulation and provide guidance for future studies of individual differences in this domain.