Emanuel, Robyn M.

Abstract Background Patients with cancer may face a significant knowledge deficit as they battle their illness. We developed a first of its kind comprehensive patient symposia (Living with Cancer (LWC): A Mayo Clinic Symposia for Patients and Loved Ones) with 8 hours of general sessions (covering nutrition, exercise, cancer inheritance, financial and legal challenges, communication, survivorship, and cancer therapy) and a 4-hour disease specific breakout (myeloid diseases, myeloma, lymphoma, chronic lymphocytic leukemia, breast cancer, lung cancer, cutaneous malignancy, colorectal cancer, and prostate cancer). Through voluntary questionnaires, we studied the impact of this cancer symposium on quality of life, cancer specific knowledge, and symptom management among cancer patients. Methods LWC meeting attendees were provided surveys prior to and 3 months following the convention. Surveys included 1) EORTC-QLQ-C30; 2) new disease understanding tool developed specifically for this conference; 3) distress thermometer and problems checklist; 4) validated disease-specific questionnaires. Changes over time were assessed using McNemar’s tests and paired t-tests for categorical and continuous variables, respectively. Results Patients:158 attendees completed the pre-convention survey. The median age was 67.5 (range 30-86), 49% males, 76% over 1 year from diagnosis. Cancer type included 37% hematologic malignancies, 23% breast cancer, 23% prostate cancer, and 17% other. The hematologic malignancies were comprised of 34% leukemia, 31% CLL/lymphoma, 25% amyloid/multiple myeloma, and 9.3% myeloproliferative neoplasms. Baseline Disease Understanding, Symptoms, QOL: Most attendees endorsed understanding their disease quite a bit (54%) or very much (29%). Most respondents reported at least “quite a bit” of understanding regarding treatment options (84%), screening modalities (83%), symptomatology (74%), and cancer-related side effects (71%). Attendees endorsed the least understanding of disease-related stress (49%), risk factors (49%), management of disease related fatigue (41%), and legal issues related to disease/treatment (27%) Mean QLQ-C30 scores were 84.4 for physical functioning, 83 for role functioning, 80.7 for social functioning, and 72.7 for global health status. The symptoms with highest mean scores were insomnia, fatigue, and pain. Knowledge Improvement Durable at 3 Months: 115 (73%) patients completed the post-symposium survey. There was improvement in 12 of 14 areas of self-reported knowledge (Table 1) especially in areas of nutrition, and management of disease related stress and fatigue (all p<0.001). Symptomatic Changes at 3 Months: There was no significant change in QLQ-C30 physical/role/emotional functioning, fatigue, pain, or insomnia. Conclusions This first evaluation of a patient centered cancer symposium as an education intervention suggests patients selecting to participate in such an event seek to improve an already solid knowledge base regarding their malignant disease. Participating in the event improved disease specific knowledge in numerous areas. However, as a single intervention, function and symptoms tended not to improve with participation. Future efforts on 1) improving participation with disease knowledge “naïve” patients and 2) targeted efforts aimed at specific symptom management (i.e. insomnia, stress) are planned. This study serves as an avenue to empower patients and inform physicians to improve the experience of living with cancer. Disclosures: No relevant conflicts of interest to declare.

Abstract Background Symptom burden among MPN patients is severe compared to age-matched controlled and other individuals with cancer. MPN-Related Fatigue (MRF) is among one of the most frequent and debilitating of symptoms among MPN patients and contributes greatly to the loss of quality of life. To date, little is known regarding the breadth and efficacy of strategies to reduce or palliate MRF. Methods A 17-item internet-based survey was hosted on the MPN Forum website during February of 2013. The survey included data on demographics, type of fatigue (chronic, sporadic, or both), strategies to reduce fatigue, and symptom burden using the MPN-SAF TSS. The MPN-SAF TSS also included a validated 1-item measure to assess worst fatigue in the last 24 hours (scored on a 0 (absent/as good as it can be) to 10 (worst-imaginable/as bad as it can be) scale). Results 879 MPN patients responded to the online survey. The majority of patients had been diagnosed with their MPN for more than one year (5.8% less than one year, 34.4% one to five years, 30.3% five to ten years, and 27.6% more than 10 years). Mean age of MPN diagnosis was 49.3 (range 12-84). A near equal mix was seen of chronic (35.3%), sporadic (29.9%) and both chronic and sporadic fatigue (28.8%). Average symptom burden was very severe (mean MPN-SAF TSS =31.9), with an average worst 24-hr fatigue rated as 5.9/10. Many strategies to reduce MPN-related fatigue were mentioned via open and categorical responses (Table 1). Exercise was the most commonly mentioned fatigue reduction strategy, followed by diet and social interaction. Diet strategies included the consumption of fruits and vegetables and using foods to combat specific nutrient deficiencies (e.g., iron). Interventions to increase rest included obtaining >8 hours of sleep at night, taking frequent naps if needed, and strategically timing naps (e.g., sleeping prior to activity). Timing strategies were implemented to maximize energy levels, including scheduling activities at time periods during the day when patients felt most awake. Stress-reduction strategies included massages, meditation and yoga. Some respondents felt work was both source of energy and motivation, although others mentioned cutting back work hours or obligations in order to reduce fatigue. New activities such as gardening and enjoying the outdoors were also mentioned. Use of non-prescription supplementation, including caffeine and over-the counter energy supplementation, was common. Prescription energy stimulants included MPN-specific treatments (e.g., ruxolitinib, hydroxurea, ASA, interferon), steroids, noradrenergic stimulants (e.g., methyphenidate, modafinil), prescription vitamin supplements (e.g., vitamin B12 injections), erythropoietin analogues, and blood thinners. Conclusions Overall patients were very symptomatic of disease (previously reported MPN-SAF TSS scores 18.7 ET, 21.8 PV, and 25.3 MF) and worst 24-hr fatigue (previously reported as 4.0 ET, 4.4 PV, and 5.0 MF) than previously published MPN cohorts (JCO 2012 20;30(36):4590). Many intervention strategies are utilized to reduce MRF. Future trials investigating pharmacologic, psychosocial, and activity-related interventions to reduce MRF are needed. Disclosures: Harrison: NOVARTIS: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; YM Bioscience: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene: Honoraria; Shire: Speakers Bureau; Sbio: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity’s Board of Directors or advisory committees.

Abstract Abstract 1731 Background: Symptom burden in primary, post-ET and post-PV myelofibrosis (MF) is frequently severe and correlates with a poor prognosis. However, symptom manifestations are heterogeneous with variable presence of specific symptoms, splenomegaly and cytopenias. We sought to identify the spectrum and features of MF symptomatic phenotypes by cluster analysis of prospectively gathered information on MF symptoms and disease features. Methods: Data was collected among an international cohort of subjects with MF. Data included demographics, disease features and completion of the Brief Fatigue Inventory (BFI) and Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) (Blood 2011; 118:401–408). Surveyed symptoms addressed key disease features on a 0 (absent) to 10 (worst-imaginable) scale. Cluster development was based on consideration of r-squared in hierarchical clustering using Ward's linkage. Final cluster assignment was based on the nonhierarchical k-means method. Comparisons between symptom clusters were based on ANOVA and chi-squared tests. Results: Subject Demographic and Disease Characteristics: Data from 329 prospectively enrolled persons with MF was collected (Chinese 102, French 54, German 19, Italian 22, Dutch 45, English 51, Spanish 29, Swedish 7) including 223 PMF, 67 post-ET MF and 39 post-PV MF patients. Participants were of typical age (mean 59) and gender (47% F). Among all participants, four natural symptom clusters were identified (Figure 1). Among clusters, disease features including leukopenia, thrombocytopenia, and enlarged spleen varied significantly between clusters (P<0.05). Cluster 1: The “Fatigue Dominant with Few Lab Abnormalities” Profile (n=150 (46%; 69% PMF, 20% post-ET MF, 11% post-PV MF)). Cluster 1, the largest, is characterized by fatigue-dominant complaints in the setting of the lowest overall MPN-SAF TSS and highest proportion of males (59%). Individuals among this group have the lowest prevalence of laboratory abnormalities (65% total; anemia, 67%; thrombocytopenia, 20%) or clinical deficiencies including enlarged spleen (average 6.0 cm below costal margin), prior thrombosis (9%), prior hemorrhage (5%) or prior RBC-transfusions (20.4%). Interestingly, individuals in this group are most likely to have had prior splenectomy (5.8%). Cluster 2: The “Cognitive Complaints with Enlarged Spleen” Cluster (n=105 (32%; 65% PMF, 20% post-ET MF, 15% post-PV MF)). Cluster 2 is the 2nd largest cluster. Subjects have relatively few abnormal lab values (67% vs 65%–77%) but have high severity of fatigue, sexual difficulties, insomnia, inactivity and reduced QOL. These individuals have the largest spleen size (8.7cm below costal margin). Cluster 3: The “Nighttime and Cognitive Complaints” Group (n=53 (16%; 64% PMF, 25% post-ET MF, 11% post-PV MF)). Cluster 3 is the smallest cluster. Subjects have many cognitive and nighttime-related complaints including sexual difficulties, night sweats, insomnia, and concentration problems. Subjects with post-ET MF are predominant. This cluster also has the 2ndsmallest spleen size (7 cm) or history of prior thrombosis (9.6%), hemorrhage (7.8%) or requirement for transfusions (21.2%). Cluster 4: The “Severe Fatigue with Few End-organ Complaints” Cluster (n=21 (6%; 81% PMF, 14% post-ET MF, 5% post-PV MF)). Cluster 4 is the most symptomatic cohort with the highest proportion of subjects with PM. There is a lower frequency of end-organ complaints including abdominal pain, cough, and headaches. Symptoms including sexual difficulties, sad mood and insomnia are predominant. No subjects had prior splenectomy. Subjects also have the highest prevalence of prior thrombosis (29%), hemorrhage (14%), and transfusions (43%). Additionally, this cohort has the largest prevalence of lab abnormalities (77%) with thrombocytopenia (71%), leukopenia (41%) and anemia (41%). Conclusion: This analysis will allow us to examine a new framework for evaluating persons with MF using symptom profiles and is the 1st cluster evaluation of MF. Lab and physical findings contrast significantly between symptom clusters indicating these phenotypic symptoms likely result from etiological factors present in specific disease phenotypes. Future studies should evaluate whether there is a correlation between cluster profiles, prognosis and genotype. Disclosures: Kiladjian: Celgene: Research Funding; Novartis: Honoraria, Research Funding; Shire: Honoraria. Roy:Novartis, BMS: Speakers Bureau. Harrison:Novartis: Honoraria, Research Funding, Speakers Bureau; YM Bioscience: Consultancy, Honoraria; Sanofi Aventis: Honoraria; Shire: Honoraria, Research Funding. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees. Passamonti:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Mesa:Incyte: Research Funding; Lilly: Research Funding; Sanofi: Research Funding; NS Pharma: Research Funding; YM Bioscience: Research Funding.

Abstract Abstract 1739 BACKGROUND: Differences in symptom burden characteristics between persons of European and non-European descent with BCR-ABL negative MPNs including essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (MF) are not studied. We reported significant clinical and laboratory differences between these populations age at diagnosis and survivals (Blood 2011;119: 2469–73) which could affect symptom burden. Given China represents one-fifth of the global population, we aimed to evaluate MPN symptom burden among a cohort of Chinese MPN patients. METHODS: Data were collected from Chinese with MPNs and their physicians and compared these to a previously collected data from a cohort of subjects of predominately European descent (N=1488). Subject data included MPN-SAF (Blood 2011;118:401-8) and BFI score (Cancer 1999;85: 1186–96), demographics, and disease-related features. Statistical methods included ANOVA, chi-squared tests, and multiple regressions. RESULTS: Demographic and Disease Characteristics: 397 Chinese subjects were prospectively enrolled with a distribution of 172 (43%) ET, 102 (26%) PV, and 123 (31%) MF (of which 103 [84%] were PMF, 14 [11%] were post-ET MF, and 6 [5%] were post-PV MF). Median age (56.0 y) was younger in Chinese than in the European-descent cohort (63.0 y, p<0.001) despite relative gender equality. Laboratory abnormalities including anemia (76%, p<0.001) and disease features including bleeding (1%, p<0.001), were more common and present at a significantly higher incidences in the European-descent cohort than amongst Chinese. Chinese Symptom Severity and Incidence by MPN type: When comparing across MPN types, symptoms of worst fatigue, early satiety, abdominal discomfort, inactivity, concentration, depression, cough, night sweats, weight loss, and total MPN-SAF TSS score varied significantly (p<0.05) with MF being most severe for each symptom. Chinese versus European-descent Symptom Severity: After adjusting for age and MPN type, Chinese subjects had significantly higher mean severity for fever, sexual difficulties, and quality of life (Table 1). Symptoms of worst fatigue, early satiety, abdominal discomfort and overall BFI score had a significantly higher mean severity in the European descent cohort. Chinese versus European-descent Symptom Incidence: The European-descent cohort had significantly greater incidence of worst fatigue (90% vs 81%, p<0.001), abdominal pain (47% vs 35%, p<0.001), early satiety (65% vs 57%, p=0.005), concentration problems (64% vs 58%, p=0.04), numbness (63% vs 56%, p=0.02), insomnia (68% vs 58%, p<0.001), and depression (62% vs 56%, p=0.02) compared to Chinese subjects. In contrast, symptoms of dizziness (63% vs 57%, p=0.04), sexual difficulties (72% vs 61%, p<0.001), and fever (23% vs. 18%, p=0.03) were significantly worse amongst Chinese. CONCLUSION: We found a significant divergence in severity and incidence of key symptom burdens including QOL, fever, sexuality, dizziness, abdominal pain, early satiety, and fatigue between Chinese and persons of European descent with MPNs. Biological and cultural factors likely account for these differences and should be considered when interpreting outcomes of clinical trials of diverse populations. When the target of therapy is reversing symptoms, the best strategy may require revision for different populations. Disclosures: Mesa: Incyte: Research Funding; Lilly: Research Funding; Sanofi: Research Funding; NS Pharma: Research Funding; YM Bioscience: Research Funding.

Abstract Abstract 2852 Background: The 18-item Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF, Scherber et al Blood 2011) given in conjunction with the 9-item Brief Fatigue Inventory (BFI, Mendoza et al Cancer 1999) is a patient-completed questionnaire for assessing symptoms in persons with MPNs. The MPN-SAF has been translated and validated in 9 languages to date. The Total Symptom Score (TSS) is computed from 10 of the most pertinent MPN-SAF items to assess symptom burden in MPN patients and to evaluate response to therapy. Psychometric properties of the TSS have been previously reported (Emanuel et al Blood 2012). The purpose of this analysis is to compare MPN-SAF symptoms and psychometric properties of the TSS across 9 languages in an international sample. Methods: Data were collected in an international cohort of subjects with MPNs. Surveyed symptoms included fatigue, early satiety, abdominal pain and discomfort, inactivity, headaches, concentration, dizziness, extremity tingling, insomnia, sexual problems, mood changes, cough, night sweats, pruritus, bone pain and fever on a 0 (absent) to 10 (worst imaginable) scale. TSS was computed using the published scoring algorithm on a 0 (all symptoms absent) to 100 (all symptoms worst imaginable) scale. Demographic and disease-related data including disease type, gender, and age had to be present to be included in analysis. Demographics were compared across languages groups using ANOVA and chi-squared tests. Symptoms and TSS were compared across language groups using a general linear model adjusting for disease type, age, and gender with post-hoc Tukey pairwise comparisons. Internal consistency and factor structure of the TSS were investigated overall and within language groups using Cronbach's alpha and principal-axis factoring analysis. Results: Subject Demographics and Disease Type: 1,851 subjects with polycythemia vera (PV N=655), essential thrombocythemia (ET N=769) and myelofibrosis (MF N=427; 286 primary MF, 61 PV-MF, 80 ET-MF) were prospectively enrolled and administered the MPN-SAF and BFI in 1 of 9 languages: English [UK] 55, English [US] 102, Italian 186, Swedish 114, German 112, French 457, Spanish 192, Dutch 236, and Chinese 397. Age (median 61, range, 15–94) and gender (55% F) were typical. Disease type and age varied across language groups (both p <0.001). MPN-SAF Symptoms and TSS: Symptom frequencies ranged from 19% (fever) to 88% (fatigue) overall with mean severities ranging from 0.4 (SD=1.3, fever) to 4.3 (SD=2.3, fatigue). Fatigue had the highest mean severity among all symptoms within each language group. Overall, mean TSS was 21.5 (SD=16.7) with the Swedish (mean=18.1, SD=15.2) and Dutch (mean=27.6, SD=17.1) cohorts reporting the lowest and highest unadjusted TSS means, respectively. When comparing symptom items across languages (adjusting for disease type, age, and gender), concentration and sexual problems had the most statistically significant pairwise differences (11 and 10, respectively, out of a possible 36) followed by dizziness and overall quality of life (9 each, out of a possible 36). No statistically significant pairwise differences were observed for abdominal discomfort, headache, extremity tingling, or insomnia. For the TSS, the Dutch cohort appeared to statistically significantly differ (all p <0.05) with all other languages except the English cohorts. All other TSS pairwise comparisons were not statistically significant. TSS Internal Consistency and Factor Structure: The TSS had excellent internal consistency overall (Cronbach's alpha 0.83) as well as within language groups (Cronbach's alpha 0.81–0.86). Overall factor analysis identified a single underlying construct among the 10 TSS items. Factor loadings ranged from 0.41 for fever to 0.73 for inactivity. A single factor solution was appropriate for each language group with factor loadings ranging from 0.18 to 0.85. Conclusion: This analysis suggests that the available translations of the MPN-SAF are generally acceptable for use in a broad context. The TSS demonstrated acceptable internal consistency and similar factor structure across all language groups. Most symptom and TSS comparisons between languages were not statistically significant, but for the few which differed, further studies are needed to evaluate whether these variances are due to disease-related factors or due to linguistic or cultural influences present in the cohorts. Disclosures: Kiladjian: Novartis: Honoraria, Research Funding; Celgene: Research Funding; Shire: Honoraria. Griesshammer:Shire: Honoraria. Roy:Novartis, BMS: Speakers Bureau. Harrison:Novartis: Honoraria, Research Funding, Speakers Bureau; YM Bioscience: Consultancy, Honoraria; Sanofi Aventis: Honoraria; Shire: Honoraria, Research Funding. Passamonti:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Mesa:Incyte: Research Funding; Lilly: Research Funding; Sanofi: Research Funding; NS Pharma: Research Funding; YM Bioscience: Research Funding.

Abstract Abstract 1726 Background: We previously reported that symptom burden among persons with ET and PV can be severe and adversely affect QOL. The presence of severe symptoms is linked to poor prognosis. There is considerable inter-subject heterogeneity regarding which symptoms are present in which subjects. No studies have empirically evaluated whether disease characteristics can be grouped in related symptom clusters. Using our previously validated 18 item Myeloproliferative Neoplasm Assessment Form (MPN-SAF) (Blood 2011;118:401–408) given in conjunction with the 9 item Brief Fatigue Inventory (BFI) (Cancer 1999;85:1186–1196), we sought to evaluate symptom burden by means of cluster analysis. Methods: Data was collected from an international cohort of subjects with MPNs including demographics, disease features and the completed BFI and MPN-SAF instruments. Surveyed symptoms included fatigue, early satiety, abdominal pain and discomfort, inactivity, headaches, concentration, dizziness, extremity tingling, insomnia, sexual difficulties, mood changes, cough, night sweats, pruritus, bone pain and fever on a 0 (absent) to 10 (worst-imaginable) scale. Development of symptom clusters was based on consideration of r-squared in hierarchical clustering using Ward linkage. Final cluster assignment was based on the nonhierarchical k-means method. Comparisons between symptom clusters were based on ANOVA and chi-squared tests. Results: Subject Demographic and Disease Characteristics: Data from 1,141 subjects with PV (N=519) and ET (N=622) was prospectively collected (Chinese 236, French 305, German 45, Italian 114, Dutch 191, English 56, Spanish 109, Swedish 85. Age (mean 59, range, 26–87) and gender (54% F) were typical. Five clusters were selected (Figure 1). Frequencies of prior bleeding, spleen size, anemia, presence of any lab abnormality, language, gender, and MPN type varied significantly between clusters (P<0.05). Cluster 1: The “Reduced Symptom” Profile (n=421 (37%; 60% ET, 40% PV) The largest cluster, subjects had increased complaints of sexual difficulties and fatigue. There was a slightly higher proportion of subjects with ET (60%) versus PV. There were fewer lab abnormalities (28% prevalence) and less prior bleeding (3%) compared to other clusters. Spleen size was smallest of the cluster (1 cm below costal margin). Cluster 2: The “Fatigue-dominant” Group (n=286 (25%; 56% ET, 44% PV)). Subjects in this cluster were predominantly female and had relatively few laboratory abnormalities (19%) than other cohorts. They are characterized by high severity of fatigue compared to end-organ symptoms. Symptom profiles emphasize fatigue, QOL and insomnia with some end-organ complaints. The cohor 63% of the cohort. Cluster 3: The “End-Organ Complaints” Group (n=210 (18%; 49% ET, 51% PV)). Male predominant (56%), subjects had mainly macro-vascular symptom complaints including sexual difficulties, insomnia, and overall QOL, with few microvascular related symptoms (low itching/night sweats). Cluster 4: “Cognitive Complaints” Cluster (n=110 (10%; 53% ET, 47% PV)). The smallest cluster and female predominant (64%), main complaints include fatigue, insomnia, loss of concentration, numbness, and sad mood. Cluster 5: The “Highly Symptomatic” Cluster (n=114 (10%; 44% ET, 56% PV)). Subjects had many cognitive complaints and symptoms correlated with severe micro-vascular abnormalities (pruritus) and or splenomegaly. This cluster had the largest spleen sizes (mean 3 cm), the highest prevalence of prior thrombosis (29%), and highest frequency of lab abnormalities (43%). Cognitive and end-organ complaints were rated as most severe. Conclusion: This analysis offers new means of evaluating persons with PV and ET utilizing symptom clusters. Laboratory and physical abnormalities differed significantly between symptom clusters indicating that our groupings likely result from biological alterations present in specific disease phenotypes. Future studies should investigate correlations between clusters and prognosis and genotype. Disclosures: Kiladjian: Celgene: Research Funding; Novartis: Honoraria, Research Funding; Shire: Honoraria. Roy:Novartis, BMS: Speakers Bureau. Harrison:Novartis: Honoraria, Research Funding, Speakers Bureau; YM Bioscience: Consultancy, Honoraria; Sanofi Aventis: Honoraria; Shire: Honoraria, Research Funding. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees. Passamonti:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Mesa:Incyte: Research Funding; Lilly: Research Funding; Sanofi: Research Funding; NS Pharma: Research Funding; YM Bioscience: Research Funding.

Abstract Abstract 1736 Background: Histone deacetylase inhibition (HDACi) has shown a potent inhibitory activity on the autonomous proliferation of hematopoietic cells of PV and ET patients carrying the JAK2V617F mutation (Leukemia. 2008;22(4):740–7). Hematological responses have been recorded during treatment with the HDACi givinostat in patients with PV and myelofibrosis (Blood. 2011; 118:a1748). Additionally, combinational use of givinostat and hydroxyurea (HU) have shown encouraging clinical response in PV (Br J Haematol. 2010;150:446–55). Recent laboratory studies of vorinstat-treated JAK2V617F knock-in mice have observed normalization of peripheral blood counts, markedly reduced splenomegaly and decreased mutant allele burden (Blood 2012; 119, 3779–89). Despite this evidence of hematologic response, to date no studies have evaluated specific changes in symptom burden among PV and ET patients treated with HDACi. METHODS ET and PV patients from the UK were enrolled in a non-randomized, open-label phase II multicenter study of the HDACi vorinostat (Haematologica 2011;96(s2):a1023). Patients were asked to complete the 18 item Myeloproliferative Neoplasm Assessment Form (MPN-SAF) (Blood 2011;118:401–408), 9 item Brief Fatigue Inventory (BFI) (Cancer 1999;85:1186–1196) and 30 item EORTC QLQ-C30 (J Natl Cancer Inst 1993; 85(5):365-76) at enrollment, week 12, week 24, and week 36. From weeks 1 through 24, participants were given 400mg of vorinostat daily and were observed from weeks 24 to 36. RESULTS Participant Demographics and Mutational Status: 15 PV and 10 ET patients were enrolled in the study. Median age of participants was 65 and 48% of participants were female. JAK2 mutations were present in 5/10 (50%) of ET and 14/15 (93%) of PV patients. Change in Symptom Severity with Vorinostat: Although most symptom severity changes did not reach statistical significance likely due to the small sample size, individual symptoms of headache (mean 1.6 baseline to 0.5 wk 36, mean maximum improvement 0.5 from baseline), dizziness (mean 1.6 baseline to 0.9 wk 36, mean maximum improvement 0.6 from baseline), sad mood (mean 2.6 baseline to 1.9 wk 36, mean max improvement 0.2 from baseline), and bone pain (mean 2.7 baseline to 0.8 wk 36, mean max improvement 0.7 from baseline) indicated consistent reductions in severity. Change in Symptom Incidence with Vorinostat: Non-sustained reductions in symptom incidence were seen with initiation of therapy for items of dizziness (50% baseline, 43% wk12, 55% wk 24, and 38% wk 36), numbness (65% baseline, 38% wk 12, 36% wk 24, 63% wk 36), sad mood (55% baseline, 47% wk 12, 40% wk 24, 50% wk 36), and itching (65% baseline, 50% wk 12, 40% wk 24, 75% wk 36). Change in MPN-SAF TSS Score with Vorinostat: Overall, MPN-SAF TSS did not vary significantly for the cohort over the course of the study (score change −.4 week 12, −0.5 week 24, −1.2 week 36, Figure 1). However, 9/17 participants who had a TSS of at least 6 at baseline had an overall improvement of at least 6 points (a moderate improvement) on at least one assessment after baseline. Of these, 5 of those 9 participants had an improvement of at least 10 points, which constitutes a large improvement in symptom burden based on a distributional definition of clinical significance using the standard deviation from a previous cohort. CONCLUSION This study represents the first analysis of symptom burden among PV and ET patients receiving vorinostat to date. In addition to previously identified changes in clinical and hematologic response, reductions in symptom burden including QOL and fatigue were observed in patients receiving vorinostat therapy which was most noticeable in patients with high baseline burden. The toxicity profile of vorinostat also suggests that better results might have observed if individualized assessment of clinicohematological responses including an integrated a marker for response into daily clinical practice and tailoring pharmacotherapy based on side effect profile (Leukemia. 2012;26(5):1148–9). Although further investigation among larger cohorts is needed, preliminary data is encouraging for successful therapeutic use of vorinostat in a clinical setting and with possible combinational therapy to reduce symptom burden among PV and ET patients. Disclosures: Harrison: Novartis: Honoraria, Research Funding, Speakers Bureau; YM Bioscience: Consultancy, Honoraria; Sanofi Aventis: Honoraria; Shire: Honoraria, Research Funding. Mesa:Incyte: Research Funding; Lilly: Research Funding; Sanofi: Research Funding; NS Pharma: Research Funding; YM Bioscience: Research Funding.

Abstract Background We have previously reported on the high prevalence and severity of challenges with intimacy and sexuality amongst a large international cohort of MPN patients (Emanuel JCO 2012). We sought to further analyze the relationships between issues of intimacy (sexual desire and function), their relationships to MPN disease features, individual MPN symptom prevalence and severity, language, and overall quality of life. Methods Data was collected among an international cohort of patients with MPNs. Subjects completed the BFI, MPN-SAF, and EORTC QLQ-C30 instruments. Surveyed symptoms on the MPN-SAF included the patient’s perceptions of common MPN-related symptoms and overall quality of life (QOL) on a 0 (absent) to 10 (worst imaginable) scale. Specifically, the MPN-SAF sexuality item asked about “problems with sexual desire or function”. Total symptom score (TSS) was computed based on 10 symptom items using the published scoring algorithm on a 0 (all reported symptoms absent) to 100 (all reported symptoms worst imaginable) scale. Pairwise associations between the MPN-SAF sexuality item and continuous and categorical covariates were investigated using Pearson correlations and analysis of variance/t-tests, respectively. Multivariate regression models were used to investigate impact of groups of covariates on the sexuality item with the final multivariate model selected using forward regression. Results Demographics A total of 1908 MPN patients (essential thrombocythemia=799, polycythemia vera=671, myelofibrosis=432, missing=6) completed the sexuality item. Participants were of typical age (median=60, range 15-94) and gender (female=53%). Overall, 1218 subjects described sexuality related complaints (score >0) with an overall mean symptom score of 3.5 (median=2.0, SD=3.7, range 0-10); 725/1908 (38%) patients had severe sexuality related complaints (score >4). Univariate Analysis Among the QLQ-C30 functioning scales, all domains had similar statistically significant correlations (r=-.26 to -.32, all p<0.001). Among QLQ-C30 symptom scales, all QLQ-C30 symptoms displayed correlations ranging between .08 and .29 (all p<0.001). Among MPN-SAF items, the MPN-SAF sexuality item correlated most significantly with the TSS (r=.41, p<0.001), along with MPN-SAF symptoms (r=.16 to .39; all p<0.001). MPN-SAF sexuality measure significantly differed by anemia (means: absent 3.3, present 4.5; p<0.001), leukopenia (means: absent 3.4, present 4.4; p=0.01), thrombocytopenia (means: absent 3.3, present 4.5; p<0.001), red cell transfusion (means: no 3.5, yes 5.0; p<0.001), MPN subtype (ET mean 3.1, PV mean=3.6, MF mean=4.4; p<0.001) and language (means ranged from 2.4 [Swedish] to 4.6 [Chinese]; p<0.001). MPN-SAF sexuality did not significantly differ by age, gender, prior thrombosis or prior hemorrhage. Multivariate Analysis In a multivariate model of MPN-SAF sexuality containing all QLQ-C30 functioning scales, physical (p=0.001), emotional (p=0.01), cognitive (p=0.005) and social (p=0.002) functioning were all statistically significant. Numerous symptoms were also significant in a multivariate model of MPN-SAF sexuality containing all other MPN-SAF symptoms (all p<0.05; abdominal pain, inactivity, dizziness/vertigo/lightheadedness, insomnia, depression/sad mood, cough, night sweats and overall QOL). The final multivariate model based on forward regression starting with all demographics, clinical variables, and patient-reported QLQ-C30 scales and MPN-SAF items found age, language, QLQ-C30 role functioning and MPN-SAF items (insomnia, depression/sad mood, night sweats and QOL) to be significant (p<0.05). Conclusions Sexuality related complaints have been linked to both physiologic and psychologic origins and are highly prevalent within the MPN population. The results of this study congruently identified close associations between sexuality and function within emotional, cognitive and social domains. Additionally, the correlations of sexuality issues with MPN symptoms and disease features further suggest this item is a key correlate of overall functionality and quality of life. Future investigations into the causative factors and biological correlates of this complaint may assist in addressing this ongoing challenge. Disclosures: Etienne: novartis: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Pfizer: Membership on an entity’s Board of Directors or advisory committees; Ariad: Membership on an entity’s Board of Directors or advisory committees. Roy:Novartis, BMS: Honoraria. Harrison:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; YM Bioscience: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene: Honoraria; Shire: Speakers Bureau; S Bio: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Birgegard:Vifor Pharma: Honoraria. Mesa:Eli Lilly and Co: Research Funding; Genetech: Research Funding; Gilead: Research Funding; Incyte: Research Funding; Sanofi: Research Funding; NS pharma: Research Funding; Celgene: Research Funding.

Abstract Introduction Myelofibrosis (MF) and Post PV/ET MF represents a group of debilitating hematological disorders in which quality of life (QOL) is severely compromised in most patients as a result of persistent constitutional symptoms, progressive cytopenias, and splenomegaly. Conventional therapeutic modalities have largely focused on symptoms palliation rather than cure. Allogeneic stem cell transplantion (ASCT) remains the only potential curative option for intermediate and high risk disease. Till now, outcome data for MF have historically focused on survival benefit. Until now, few studies have evaluated the QOL, financial burden, and symptom response in MF patients undergoing treatment including ASCT. The development of the Myeloproliferative Symptom Assessment Form Total Symptom (MPN-SAF TSS) score in 2012 allows us to objectively quantify with a standardized tool these crucial aspects of patients care. The Myeloproliferative Neoplasm Quality of Life (MPN-QOL) Study Group aims to objectively quantify symptomatic response to standard available treatments by utilizing the MPN-SAF TSS. We introduce two MPN-QOL prospective trials currently in active enrollment: The MPN Experimental Assessment of Symptoms by Utilizing Repetitive Evaluation (MEASURE) Trial and the Symptoms Yielded in Myelofibrosis Patients after Transplant as Objectified by MPN-SAF TSS (SYMPTOMS) Trial. Our intention with these studies is to quantify the QOL and symptom burden of PMF and post PV/ET MF patients undergoing treatment including ASCT. Methods The MEASURES trial is a prospective questionnaire based study evaluating the responsiveness of the MPN-SAF TSS in detecting symptomatic changes in target symptoms for an anticipated 180 ET, PV and MF (including primary MF, post-ET and post PV MF) patients receiving non-experimental medical therapy (aspirin, hydroxyurea, anagrelide, interferon, busulfan, melphalan, cladribine, thalidomide, lenalidomide, prednisone, danazol, ruxolitinib) and/or phlebotomy. Patients complete the MPN-SAF for seven consecutive days at the time of enrollment and repeat the survey for an additional seven consecutive days between 90 days and six months. Patients also complete the MDASI, EORTC and Global Impression of Change Items on the first day of the second assessment. Physicians acquire demographic, laboratory, physical examination and radiographic data, along with serial response assessments. In parallel, the SYMPTOMS trial is prospective questionnaire based study evaluating the QOL of patients undergoing ASCT utilizing MPN-SAF TSS, the FACT-BMT, Global Impression of Change, and a financial questionnaire. Patients will be evaluated at various time points pre-transplant, day 30, day 100 and 1 year post-transplant. Participants (N=110) will be prospectively enrolled from Mayo Clinic Arizona (MCA) with other centers to soon join. To date we have enrolled 5 patients from MCA on the SYMPTOMS trial and 32 patients on the MEASURES trial. Results Both trials began open enrollment in the summer of 2012 and remain in recruitment phase. Our updated preliminary data will be presented at the ASH 2013 meeting Conclusion Myeloproliferative Neoplasms have been associated with debilitating symptom profile that can significantly impair the QOL. We recognize the burden of this disease and treatment and have therefore initiated two ongoing parallel prospective trials with goals to quantify the QOL and symptom burden of MPN patients. By quantifying degree of burden and impairment in QOL in a standardized format in MPN patients undergoing a range of treatments, we will in the future be better able to inform our patients of the likely benefits and toxicities of the available treatment options. Disclosures: Birgegard: Vifor Pharma: Honoraria.

Abstract Background We have previously reported on the high prevalence and severity of insomnia amongst a large international cohort of MPN patients (Emanuel JCO 2012). We sought to further analyze the relationships between insomnia and the MPN disease features (in particular splenomegaly, status of blood counts), individual MPN symptom prevalence and severity, language, and overall quality of life. Methods Data was collected among an international cohort of patients with MPNs. Subjects completed the BFI, MPN-SAF, and EORTC QLQ-C30 instruments. Surveyed symptoms on the MPN-SAF included the patient’s perceptions of common MPN-related symptoms and overall quality of life (QOL) on a 0 (absent) to 10 (worst imaginable) scale. Specifically, the MPN-SAF insomnia item asked about “difficulty sleeping”. Total symptom score (TSS) was computed based on 10 symptom items using the published scoring algorithm on a 0 (all reported symptoms absent) to 100 (all reported symptoms worst imaginable) scale. Pairwise associations between the MPN-SAF insomnia item and continuous and categorical covariates were investigated using Pearson correlations and analysis of variance/t-tests, respectively. Multivariate regression models were used to investigate impact of groups of covariates on the insomnia item with the final multivariate model selected using forward regression. Results Demographics A total of 1992 MPN patients (essential thrombocythemia=834, polycythemia vera=703, myelofibrosis=449, unknown=6) completed the insomnia item. Participants were of typical age (median=61, range-15-94) and gender (female=54%). Overall, 1307 subjects endorsed the MPN insomnia item (score >0) with an overall mean symptom score of 3.0 (median=2.0, SD=3.1. range=0-10); 603/1992 (30%) of patients had severe insomnia related complaints (score >4). Univariate Analysis Among QLQ-C30 functioning scales, emotional functioning most highly correlated with the MPN-SAF insomnia item (r=-.47, p<0.001) with all other domains also having statistically significant but slightly weaker correlation (all p<0.001). Among QLQ-C30 symptom scales, insomnia (r=.79, p<0.001) and fatigue (r=.45, p<0.001) most highly correlated with the MPN-SAF insomnia item with all other QLQ-C30 symptoms having correlations between .13 and .37 (all p<.001). Among MPN-SAF items, the MPN-SAF insomnia item correlated with all MPN-SAF items (all p<0.001) including the TSS (r=0.55, p<0.001) and most highly with depression (r=.52, p<0.001), concentration problems (r=.43, p<0.001), overall QOL (r=.41, p<0.001), night sweats (r=.41, p<0.001), and extremity tingling (r=.40, p<0.001). MPN-SAF insomnia significantly differed by gender (means: M 2.4, F 3.4; p<0.001), language (means ranged from 2.6 [Italian] to 3.6 [German]; p=0.01), anemia (means: absent 2.8, present 3.5; p<0.001), prior hemorrhage (means: no 2.9, yes 3.7; p=0.01), and requiring red blood cell transfusion (means: no 2.9, yes 3.6; p=0.03), with a trend for a difference by MPN type (ET mean=2.7, PV mean=3.0, MF mean=3.2; p=0.06). Multivariate Analysis In a multivariate model of MPN-SAF insomnia containing all QLQ-C30 functioning scales, physical, emotional, and cognitive functioning along with global health status/QOL were all significant (all p<0.001). Numerous symptoms were also significant in a multivariate model of MPN-SAF insomnia containing all other MPN-SAF symptoms (all p<0.05: headaches, extremity tingling, depression, sexual problems, night sweats, pruritus, fever, and QOL). The final multivariate model based on forward regression starting with all demographics, clinical variables, and patient-reported QLQ-C30 scales and MPN-SAF items found age, gender, QLQ-C30 emotional functioning and MPN-SAF items to be significant. Conclusions Insomnia is highly prevalent and severe in MPN patients and closely correlates with most other MPN-related symptoms and functional domains bearing a multi-faceted impact on overall quality of life. Correlations between insomnia and emotional, cognitive, and physical complaints including depression/sad mood, concentration problems, night sweats, and numbness/tingling in the extremities suggest that the cause of MPN-related sleep complaints is likely complex. Future studies should evaluate the impact of interventions on MPN associated insomnia as well as its biological underpinnings. Disclosures: Etienne: novartis: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Pfizer: Membership on an entity’s Board of Directors or advisory committees; Ariad: Membership on an entity’s Board of Directors or advisory committees. Roy:Novartis, BMS: Honoraria. Harrison:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; YM Bioscience: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene: Honoraria; Shire: Speakers Bureau; S Bio: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Birgegard:Vifor Pharma: Honoraria.