Citations

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 Background: Outcomes in multiple myeloma (MM) have improved significantly over the years but disparities in outcomes exist among MM patients (pts) belonging to different racial subgroups. Previous studies have explored healthcare access and utilization disparities for pts of different races as potential causes, but genomic differences, which could alter disease biology and clinical behavior, have not been studied. We utilized the MMRF CoMMpass database, which prospectively captures clinical and molecular characteristics of MM patients to explore race-based differences at the genomic level. Methods: The publically available CoMMpass trial database (data release version IA8) was utilized. Pts with race category of White (total n=698) and non-White (total n=223, comprising 129 Blacks, 19 Asians and 45 others) were analyzed for genomics including cytogenetics (fluorescent in situ hybridization; FISH), tumor diploidy (conventional karyotyping), gene expression profiling (GEP), gene copy number variations (CNV), gene single nucleotide variations (SNV) and genomic translocations analysis focused on genes from the FoundationOne Heme panel¨ (402 genes). GEP was considered significantly different between categories for more than or equal to a 2-fold change for a given gene (p<0.05). Categorical variables for FISH probes and diploidy status were compared by Chi-square or Fischer exact test, wherever applicable. Results: GEP clustering analysis uncovered 67 genes differentially expressed between Whites vs. non-Whites (Fig 1A). Baseline cytogenetics aberrations between both race cohorts showed statistically insignificant differences. Multiple cytogenetic abnormalities were seen most commonly in both race groups (~31%) with the distribution of others (in descending order) as such: Del13 > No abnormalities > t(11;14) > 1q amplification > Del17p or p53 > t(4;14) > Del1p > t(14;16) > t(14;20). Aneuploidy status showed insignificant differences between race groups with ~34% of patients from both groups having no aneuploidy. SNV data was present for 90% of Whites and 57% of non-Whites. Overall, 84% of genes had>1 SNV (84%), 2% translocations only and 14% had neither SNVs or translocations. SNVs were classified as Non-specific Non-Synonymous coding (NNSCs), Splice-site (SS) or Tier 1 (T1, codon deletion, insertion, frame-shift, etc.). A total of 880 NNSCs SNVs were observed: 670 in Whites across 227 genes, 210 in non-Whites across 120 genes. In whites, 57% of NNSC SNVs consisted of transition-type mutations and 43% as transversions. In non-Whites, transition mutations comprised 64% of all NNSC SNVs and transversions in the remaining 36%. A total of 38 SS SNVs were observed, 30 in Whites and 8 in non-Whites observed in 25 and 6 genes, respectively. In Whites, 57% of SS SNVs were transition type and remaining 43% were transversion. In non-Whites, an equal % of SS transition and transversion mutations were noted. A total of 240 T1 SNVs were noted; 182 in Whites seen in 82 genes; 58 in non-Whites seen 6 genes. In both Whites and non-Whites, frameshifts (41% in Whites, 47% in non-Whites) and stop-gained (46% in Whites, 45% in non-Whites) SNVs were most common. A total of 17 genes with>10 distinct SNVs were identified in Whites; 5 genes in non-Whites and 4 genes commonly seen in both cohorts (Fig 1B). In Whites, 17 genes were found to have translocations (intrachromosomal TRAF3 and PIK3R2 most common); in non-Whites, 5 genes had translocations (intrachromosomal CIC and EMSY most common). CNV analysis demonstrated 21 genes that were significantly altered with either copy number gain or loss between Whites vs. non-Whites (Fig 1C). Conclusions: We present the first race-based comprehensive genomic analysis utilizing the public interface of the CoMMpass trial. We discovered genomic differences between Whites and non-Whites at several levels including GEP, SNV and CNV, but not at the level of cytogenetics, which are in fact the most commonly performed clinical genomic analysis. Correlation of these variations with MM pt outcomes would be invaluable in understanding disease biology and hopefully mitigating some of the outcome disparities by pt race. As the database grows and becomes more enriched, separate analyses for Blacks, Asians and Hispanics would be attempted. Acknowledgments: We would like to thank the MMRF, Ms. Mary Derome and Dr. Jonathan Keats for providing scientific overview and technical support. Disclosures Fonseca: Millennium, a Takeda Company: Consultancy; Millennium, a Takeda Company: Consultancy; AMGEN: Consultancy; AMGEN: Consultancy; Patent: Patents & Royalties: Prognostication of MM based on genetic categorization of FISH of the disease; Patent: Patents & Royalties: Prognostication of MM based on genetic categorization of FISH of the disease; Patent Pending: Patents & Royalties: The use of calcium isotopes as biomarkers for bone metabolisms; Patent Pending: Patents & Royalties: The use of calcium isotopes as biomarkers for bone metabolisms; Celgene: Consultancy; BMS: Consultancy; Bayer: Consultancy; Novartis: Consultancy; Sanofi: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Millennium, a Takeda Company: Consultancy; BMS: Consultancy; AMGEN: Consultancy; Bayer: Consultancy; Patent: Patents & Royalties: Prognostication of MM based on genetic categorization of FISH of the disease; Novartis: Consultancy; Patent Pending: Patents & Royalties: The use of calcium isotopes as biomarkers for bone metabolisms; Sanofi: Consultancy; Janssen: Consultancy; Millennium, a Takeda Company: Consultancy; AMGEN: Consultancy; Patent: Patents & Royalties: Prognostication of MM based on genetic categorization of FISH of the disease; Patent Pending: Patents & Royalties: The use of calcium isotopes as biomarkers for bone metabolisms. Ailawadhi:Takeda Oncology: Consultancy; Amgen Inc: Consultancy; Novartis: Consultancy; Pharmacyclics: Consultancy.

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 BACKGROUND: The presence of constitutional symptoms has been associated with increased mortality risk in myelofibrosis (MF) (Blood 2010;115(9):1703-8). New therapies exist which alleviate the severe symptom burden profile observed in MF patients but are only approved for use in those with intermediate-2 or high risk disease (N Engl J Med 2012;366:787-798). However, it has been proposed that there are patients who may benefit from symptom based treatment regardless of prognostic score (Am Soc Hematol Educ Program 2014;2014:277-286). We have recently characterized symptom score cutoffs at which patients would statistically benefit from treatment based on symptom scores alone (Scherber et. al. EHA 2016: a2250). These treatment thresholds included aMyeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS or MPN-10) total score of greater than or equal to 20, a worst individual item score of greater than 5, or a combined criteria of those with both an MPN-10 total score of greater than or equal to 20 and a worst individual item score greater than 5. This abstract represents an additional analysis of our MF cohort to better characterize the profile of patients who meet criteria for symptom-based therapy. METHODS: Patient demographics, symptom burden via the MPN-10 score (JCO 2012;30(33)4098-103), and disease traits were collected from MF patients and their physicians at a single time point during therapy. Previously we identified MPN-10 cutoffs via AkaikeÕs Information Criterion (AIC) analysis (Ecology 2014;95: 631-6), which represented the optimal model among all models specified for the data at hand to determine which patients would most benefit from symptom-directed therapy. RESULTS: Demographics. 695 MF patients without previousruxolitinib therapy were included in this analysis. Overall, of 455 patients (65.4%) fit a cutoff of having a single worst symptom item of greater than 5/10. 401 patients (57.7%) had a MPN-10 score of equal to or greater than 20. A total of 381 (54.8%) patients fit both of these criteria. A distribution of worse MPN-10 individual scores is shown in Table 1. Mean TSS score was 26.4 (SD=17.7). Symptom Criteria Associations. Demographics and disease traits: Neither mean age or age greater than 60 was significantly associated with meeting any of the symptom score cutoff criteria. Females were significantly more likely to meet any of the symptom score cutoffs (for all criteria, p=0.0003 or less). Patients with splenomegaly, particularly spleen size of greater than 15cm below the LCM, were significantly more likely than those with a normal sized spleen to meet any of the three criteria (spleen enlargement of any size p=0.014 or less; spleen greater than 15cm p=0.0114 or less). Patients who met any of the three symptom criteria tended to have a longer MPN duration, although this trend did not meet significance. A prior history of thrombosis was not associated with achieving any cutoff criterions. Symptom burden: Individuals who met the any symptom criteria were significantly more likely to have higher DIPSS prognostic risk score (for all p=0.0002 or less). Laboratory values: For those meeting criteria for a worst symptom greater than 5, mean WBC was 11.7 vs 9.1 x 109/L (p=0.025) and platelet count was 238.7 versus 329.1 (p=0.023). For those meeting criteria for a TSS greater than or equal to 20, mean WBC was 11.8 vs 9.5 x 109/L (p=0.04). For individuals meeting both criteria, mean WBC was 11.9 vs 9.5 x 109/L (p=0.034). The presence of peripheral blasts were significantly more common in patients with an individual worst symptom score greater than 5 (p=0.0364). Hemoglobin level was not significantly associated with symptom criteria for any cutoffs. CONCLUSION: Our analysis indicates that patients who would be treated based on symptom criteria are similar to patients who would be treated based on high risk features such as high DIPSS prognostic score, concerning blood count abnormalities (i.e., leukocytosis, thrombocytopenia, presence of peripheral blasts), and splenomegaly (particularly massive splenomegaly). Thrombosis history and age were not associated with criterion cutoff assignment, and it is notable that elderly age nor history of thrombosis alone would likely alter treatment choice other than anticoagulation. This data supports that JAK2 inhibitor treatment be strongly considered in patients meeting symptom based criteria. Disclosures Dueck: Bayer: Honoraria. Kiladjian:Novartis: Honoraria, Research Funding; AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding. Zweegman:Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria, Research Funding. Schouten:Sanofi: Consultancy; Novartis: Consultancy. Etienne:ARIAD: Speakers Bureau; Pfizer: Speakers Bureau; novartis: Consultancy, Speakers Bureau; BMS: Speakers Bureau. Harrison:Shire: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Baxaltra: Consultancy, Honoraria, Speakers Bureau; Incyte Corporation: Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: travel, accommodations, expenses, Research Funding, Speakers Bureau. Radia:Novartis: Honoraria; Pfizer: Honoraria. Cervantes:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Baxalta: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AOP Orphan: Membership on an entity's Board of Directors or advisory committees. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Mesa:Promedior: Research Funding; Celgene: Research Funding; CTI: Research Funding; Gilead: Research Funding; Incyte: Research Funding; Galena: Consultancy; Ariad: Consultancy; Novartis: Consultancy.

Abstract Abstract 1517 Purpose: Decitabine, a deoxycytidine nucleoside derivative, is an inhibitor of DNA-methyltransferases indicated for treatment of myelodysplastic syndrome (MDS) including previously treated and untreated, de novo or secondary MDS of all French-American-British (FAB) subtypes, Intermediate-1, Intermediate-2, and High-Risk International Prognostic Scoring System (IPSS) groups. Laboratory evidence shows that pretreatment of AML cell lines can sensitize leukemia cells to chemotherapy as well as inhibit clonogenic potential. The purpose of this study is to evaluate the safety, pharmacokinetics, and efficacy of decitabine when used as priming before induction therapy in children with newly diagnosed AML. Exploratory analyses of genomic methylation and RNA expression patterns and minimal residual disease (MRD) are embedded correlative studies. Methods: This multicenter, randomized, two-arm, open-label study enrolls pediatric pts ages 1–16 with newly diagnosed AML to either Arm A: daunorubicin, cytarabine, etoposide (D-ADE) preceded by a 5-day course of decitabine (experimental arm) or Arm B: daunorubicin, cytarabine, etoposide (ADE; control arm). Following completion of induction on study, post-induction therapy is at the treating physician's discretion. To date, 20 pts, 10 in each arm (1–16 yrs, median 9.4 yrs in both arms) have been enrolled. Results: At the protocol-specified bone marrow sampling time 3 weeks post-induction, there were 2 CRs, 6 CRi (CR with incomplete hematopoietic recovery), 1 leukemia not in remission and 1 pt who discontinued due to an AE in Arm A. In Arm B, 6 CRs, 2CRi, 1 PR and 1 pt with marrow aplasia have been confirmed. Decitabine PK in all arm A pts (100%) were characterized by mean+SD Cmax, 297+109 ng/mL, AUC0-t, 216+73.7 ng*h/mL, CL, 136+93.9L/h, Vdss 93.1+70.7 L, t1/2 0.456+0.073 h, and median tmax0.925 h. All pts had at least one AE. Grade 3 and 4 non-hematologic AEs in Arm A that were not seen in Arm B were caecitis in 2 (20%), anorexia in 3 (30%), and hypophosphatemia in 2 (20%) of pts. All pts experienced neutropenia and thrombocytopenia as expected. One pt in Arm A had appendicitis and colon perforation on Day 6 that led to study discontinuation, later determined to have been leukemic infiltrate. Two pts have died to date (both in Arm A), one of necrotic bowel, Pseudomonas sepsis and multisystem organ failure 6 months after completing study induction therapy. One pt died 5 months following study treatment from multisystem organ failure after stem cell transplant. Epigenetic changes associated with decitabine pretreatment were analyzed and will be presented. Conclusions: Decitabine in combination with ADE chemotherapy is well tolerated in children with newly diagnosed AML. There were no AEs that had not been previously identified in adults with MDS or AML. No differences have been observed between treatment arms in hematologic toxicities based on the current sample size. To date, the decitabine-treated pts in this study may have more gastrointestinal toxicity and hypophosphatemia. Decitabine-treated pts achieved PK exposures that were similar to those observed in adults treated with decitabine. Preliminary responses by CR/CRi were similar between treatment arms; expected adverse events of neutropenia and thrombocytopenia were similar between both Arms. Molecular changes associated with decitabine pretreatment may be important in the sensitization of clonogenic AML cells. Total accrual of 40 subjects is planned. Disclosures: Off Label Use: AC220 in relapsed/refractory pediatric acute leukemia. Tarassoff:Eisai, Inc.: Employment. Jones:Eisai Inc: Employment.

Abstract BACKGROUND: Symptom burden in essential thrombocythemia (ET) and polycythemia vera (PV) is severe even among individuals with low risk disease (Blood 2012. 12;123(24):3803-10). New therapies exist which alleviate the severe symptom burden and reduce splenomegaly in ET and PV patients (N Engl J Med 2015; 372:426-435). This analysis is the first to date to evaluate thresholds at which symptom-based treatment can be considered for ET and PV patients who are intolerant or resistant to hydroxyurea (HU). METHODS: Patient demographics, symptom burden, and disease traits were collected from ET and PV patients at a single time point during therapy. The MPN-10 total symptom score (TSS, JCO 2012;30(33)4098-103) was utilized to assess symptom burden. Symptom criteria models were determined as previously described among a population of MF patients (Scherber et. al. EHA 2016: a2250). Cutoffs were then evaluated in a cohort of ET and PV patients to assess for utility as a symptom model among this population. RESULTS: Demographics and symptom burden: 838 PV and 867 ET patients with previous hydroxyurea therapy were included in this analysis. Patients were of mean age (54.9 years ET, 64.0 years PV) and gender (69.2% female ET, 55.7% female). Mean disease duration was 6.0 years for ET and 7.3 years for PV.Among ET and PV patients, 15.0% and 24.2% had prior thrombosis respectively. In evaluating prognostic risk, ET patients tended to be low (45.5%) or intermediate risk (42.9%) with only a minority of patient meeting criteria forhigh risk disease (11.6%). Laboratory findings: ET patients had a mean platelet value of 598.7x 109/L(SD=283.4). Among PV patients, mean hematocrit was 45.8% (SD=8.1) and 42.6% of patients had a hematocrit of greater than 45%. White blood cell count was normal between the two groups (ET mean 8.3 x 109/L, PV mean 9.0 x 109/L). Symptoms: Mean worst symptom severity was 6.4 out of 10 (SD=2.7). Among ET patients, worst symptom was most frequently fatigue (32.7%, mean 5.0/10, SD=3.1, overall prevalence 88%) followed by night sweats (13.6%, mean 2.0/10, SD=3.0, overall prevalence 53%) and concentration difficulties (8.6%, mean 3.1/10, SD=3.0, overall prevalence 68%). For PV, worst individual symptom items were most frequently fatigue (29.2%, mean 5.2/10, SD=3.0, overall prevalence 91%), pruritus (14.1%, mean 3.2/10, SD=3.2, overall prevalence 69%), and night sweats (12.8%, mean 2.5/10, SD=3.0, overall prevalence 57%). Cutoff Scoring: 47.0% of ET patients fit criteria for TSSgreater than to equal to 20; 59.0%% had a single itemgreater than 5; and 45.7% had both a TSS greater than or equal to 20 and a single item greater than 5. Among PV participants, 54.5% had aTSS greater than to equal to 20; 66.1% had a single itemgreater than 5; and 51.5% had both a TSS greater than or equal to 20 and a single item greater than 5. Each scoring method was significantly associated with individual item scores (Table 1). Prognostic scoring was not significantly associated with any of the symptom cutoffs evaluated. Correlations: Among ET patients, a prior history of thrombosis was significantly associated with having a worst symptom item greater than 5 (p=0.043). ET patients with lower hemoglobin were significantly more likely to meet criteria for a MPN-10 score greater than or equal to 20 or to meet combined criteria for a MPN-10 greater than or equal to 20 and single worst item greater than 5 (for both p=0.01 or less). For PV, lower hematocrit levels were significantly associated with having an individual worst symptom score of greater than 5 (44.9% versus 46.7%, p=0.0376). CONCLUSION: Assessment of ET and PV symptoms, now measurable through standardized and practical instruments such as the MPN-10, is an integral part of determining therapeutic impact of newer therapies in both clinical practice and trial settings. In our modeling, patients with severe symptom burden profiles are well represented by utilizing cutoff criteria including aworst individual symptom item of greater than 5 out of 10, an MPN-10 score of greater than or equal to 20, or combined criteria of both cutoffs. These cutoffs can be considered when determiningwhich HU intolerant or resistant patients would most benefit fromsymptom orientedtreatment. Disclosures Kiladjian: AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Research Funding. Schouten:Novartis: Consultancy; Sanofi: Consultancy. Etienne:BMS: Speakers Bureau; ARIAD: Speakers Bureau; Pfizer: Speakers Bureau; novartis: Consultancy, Speakers Bureau. Harrison:Incyte Corporation: Honoraria, Speakers Bureau; Shire: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Baxaltra: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: travel, accommodations, expenses, Research Funding, Speakers Bureau. Radia:Pfizer: Honoraria; Novartis: Honoraria. Cervantes:AOP Orphan: Membership on an entity's Board of Directors or advisory committees; Baxalta: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Mesa:Promedior: Research Funding; Celgene: Research Funding; CTI: Research Funding; Gilead: Research Funding; Incyte: Research Funding; Galena: Consultancy; Ariad: Consultancy; Novartis: Consultancy.

Abstract Introduction: Ibritumomab tiuxetan (Zevalin¨) is a radioimmunoconjugate agent that targets CD20-expressing B cell lymphomas. Currently, it is the only radioimmunoconjugate agent available on the market and is FDA approved for relapsed/refractory follicular lymphoma (FL). A retrospective study of patients with low grade FL (WHO grade 1 and 2) treated with ibritumomab tiuxetan at Mayo Clinic Florida from 2000 to 2016 was performed. Methods: The patient population consisted of previously untreated as well as relapsed low grade FL. We evaluated patient characteristics, response rate, duration of response, progression free survival, overall survival and time to next treatment. Previously untreated patients were treated with ibritumomab tiuxetan due to ineligibility for standard chemotherapy and prolonged immunotherapy, or their preference. Comparison between previously untreated FL patients treated with ibritumomab tiuxetan as the first line of treatment versus patients with relapsed FL treated with ibritumomab tiuxetan as second, third or fourth line therapy was made. Results: Low grade FL patients (n=41) that received ibritumomab tiuxetan were identified; 13 patients (32%) with previously untreated FL and 28 patients (68%) with relapsed FL. The data on response to treatment is presented in Table 1. Ibritumomab tiuxetan use in previously untreated FL was associated with more complete responses than in the relapse setting (92% vs 50% at 6 months, p=0.036). Previously untreated FL patients that received ibritumomab tiuxetan as first line therapy had better progression free survival (80% vs 35% at 3 years). Ibritumomab tiuxetan use in relapsed FL was associated with significant shorter time to relapse compared to previously untreated FL (median 1.3 years vs 4.8 years, p=0.017, figure 1) and shorter time to next treatment (65% at 4 years compared to 0% in previously untreated, p=0.007). 15% of newly diagnosed FL treated with ibritumomab tiuxetan relapsed compared to 64% of relapsed FL patient. There was no significant difference in overall survival between the two groups. The incidence of grades 3-4 neutropenia (Absolute Neutrophil Count <1000 x109/L), Anemia (Hb <8 g/dL) and Thrombocytopenia (Platelets <25 x109/L) were 47%, 7.7% and 48.7% respectively. Only 6/41 patients (15%) had cytopenias that required transfusion of blood products. More significant cytopenias were seen in relapsed group compared to previously untreated group. Conclusions: Ibritumomab tiuxetan as first line treatment in previously untreated FL patients at our institution was associated with improved response rate, better progression free survival and shorter time to next treatment when compared to its use in relapsed FL. Ibritumomab tiuxetan has significant therapeutic efficacy for both previously untreated as well as relapsed low grade FL. It was well tolerated without significant treatment-related morbidity or mortality. Moreover, treatment schedule was very convenient for the patients. Our results suggest that treatment with ibritumomab tiuxetan is an effective option for those previously untreated low grade FL patients who cannot take standard chemoimmunotherapy. Disclosures No relevant conflicts of interest to declare.

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 Background: Isatuximab (ISA) is an anti-CD38 monoclonal antibody with multiple modes of action for killing tumor cells through immune cell engagement and direct tumor targeting. In preclinical studies, pomalidomide (Pom) enhanced both the direct and indirect anti-tumor activity of ISA to a greater degree than lenalidomide (Len) (Jiang et al. Leukemia 2016). Here, we report the preliminary results of an ongoing Phase Ib dose-escalation study of ISA plus Pom and dexamethasone (Dex) in patients with relapsed and refractory multiple myeloma (RRMM) (NCT02283775). Methods: Patients with RRMM (≥2 prior MM therapies, including Len and a proteasome inhibitor) with adequate bone marrow reserve/organ function were sequentially enrolled to receive ISA 5, 10 or 20 mg/kg (weekly × 4 doses, then every 2 weeks until disease progression or intolerable toxicity) in combination with Pom 4 mg (days 1-21) and Dex 40 mg (days 1, 8, 15, and 22; 20 mg if ≥75 years old), in 28-day cycles. Pom or Dex dose reductions were permitted after Cycle 1, or during Cycle 1 in response to dose-limiting toxicities (DLTs). The primary objective was to determine the maximum tolerated dose (MTD) or recommended dose, based on the occurrence of treatment-related DLTs. Secondary objectives included evaluation of efficacy (by objective response assessment according to IMWG criteria), safety, and pharmacokinetics (PK). Results: At data cut-off (May 11, 2016), 14 patients had been treated in the first 2 dose-escalation cohorts: 8 patients at 5 mg/kg and 6 patients at 10 mg/kg. Overall, median age was 65.5 (range, 42-77) years and median time from diagnosis was 4.25 (1.0-12.5) years. Half of the patients (7/14) had received at least 5 prior regimens (median 4.5 [2-11]; prior carfilzomib in 50% of patients). Ten patients (71%) had received at least one prior stem cell transplant. Median duration of dosing was 21.2 (4-42) and 8.1 (4-12) weeks in the 5 mg/kg and 10 mg/kg cohorts, respectively, with the latter cohort also having the shortest follow-up. Three patients discontinued treatment, all in the 5 mg/kg cohort: 2 due to confirmed disease progression (discontinuation after 2 and 4 treatment cycles, respectively) and 1 due to patient withdrawal (discontinuation in Cycle 1 and patient not evaluable for response). There were no discontinuations due to treatment-emergent adverse events (TEAEs) in either cohort. Two DLTs were reported: one in the 5 mg/kg cohort (prolonged grade [Gr] 4 neutropenia), and the other in the 10 mg/kg cohort (Gr 4 neutropenic infection); both DLTs resolved with Pom dose delay/reduction. MTD has not yet been reached; the 20 mg/kg dose level is under enrollment. Overall, Gr 3/4 TEAEs were reported in 10 (71%) patients; serious TEAEs in 6 (43%) patients. The most frequent TEAEs were fatigue (64%), upper respiratory tract infection, tremor, dyspnea, and cough (29% each). The most common Gr 3/4 hematologic abnormality (laboratory assessment) was neutropenia (Gr 1, 0%; Gr 2, 7%; Gr 3, 43%; Gr 4, 43%). Gr 3/4 thrombocytopenia was reported in 4 (29%) patients (Gr 3, n=2; Gr 4, n=2). Infusion-associated reactions (IARs) occurred in 8 (57%) patients, with all cases Gr 1/2 in severity. IARs occurred during the first infusion in most patients; 3/14 (21%) patients experienced IARs at a subsequent infusion, of whom only one had IARs after Cycle 1. Of the patients evaluable for confirmed response, 8/13 (62%) achieved at least partial response (PR), and 10/13 (77%) at least minimal response (MR). At 5 mg/kg, 1 patient achieved complete response (CR), 2 very good partial response (VGPR) and 2 PR. At 10 mg/kg, 2 patients achieved VGPR, 1 PR, and 2 MR. Of the eight patients who achieved at least PR, all continued to respond without confirmed disease progression at data cut-off. The PK parameters of ISA were not affected by co-administration with Pom/Dex. Conclusions: These preliminary data suggest that the combination of ISA and Pom/Dex is generally well tolerated and clinically active in patients with heavily pre-treated RRMM. Enrollment continues and longer term follow-up from this study, including data from the 20 mg/kg cohort, will be presented. A Phase III trial to evaluate ISA plus Pom/Dex is planned. Disclosures Richardson: Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Mikhael:Sanofi: Research Funding; Celgene: Research Funding; Abbvie: Research Funding; Onyx: Research Funding. Usmani:Pharmacyclics: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Skyline: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Britsol-Myers Squibb: Consultancy, Research Funding; BioPharma: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Array: Research Funding; Novartis: Speakers Bureau. Raje:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Research Funding; Eli Lilly: Research Funding. Bensinger:Takeda: Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Research Funding; Acetylon: Research Funding; Bayer: Research Funding. Campana:Sanofi: Employment. Gao:Sanofi: Employment. Dubin:Sanofi Oncology: Employment. Wack:Sanofi: Employment. Anderson:Gilead: Membership on an entity's Board of Directors or advisory committees; Oncoprep: Equity Ownership; Oncoprep: Equity Ownership; Millennuim: Membership on an entity's Board of Directors or advisory committees; C4 Therapeutics: Equity Ownership; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Acetylon: Equity Ownership; Acetylon: Equity Ownership; Millennuim: Membership on an entity's Board of Directors or advisory committees; C4 Therapeutics: Equity Ownership; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees.

Abstract Background: Chronic GVHD contributes to morbidity and mortality after allogeneic transplantation. Several phase 2 and 3 open label studies suggested that ATLG (formerly referred to as ATG-F) reduces cGVHD without impacting relapse or survival. This report describes the first prospective randomized double blind phase 3 trial to assess the effect of ATLG (Neovii) when added to tacrolimus / methotrexate prophylaxis on cGVHD free survival. Patients and Methods: This study was conducted at 27 sites in the United States and Australia. 260 patients were randomized (132 placebo, 128 ATLG). 6 patients who were randomized never received ATLG/placebo (4 placebo and 2 ATLG). Data presented include the 128 placebo and 126 ATLG patients who underwent treatment and transplant. Patients were ages 18-65 years with a diagnosis of acute myeloid (AML, 64%) or lymphoblastic (ALL, 21%) leukemia in first or subsequent complete remission or myelodysplastic syndrome (MDS, 15%) with less than 10% marrow blasts. Median age was 48 years (18-65) with 55% males. All patients received 8/8 HLA (A, B, C, DR) allele matched unrelated products (80% mobilized peripheral blood, 20% bone marrow). Myeloablative conditioning was with cyclophosphamide and total body irradiation (Cy/TBI, 27%), busulfan and cyclophosphamide (Bu/Cy, 33%), or busulfan and fludarabine (Bu/Flu, 40%). All patients received tacrolimus starting on Day -1 and standard mtx on days 1, 3, 6, and 11 for GVHD prophylaxis. Patients received ATLG or placebo on Days -3, -2, -1 at an ATLG dose of 20 mg/kg per day (60 mg/kg total). The primary endpoint of the study was moderate/severe chronic GVHD free survival. cGVHD was scored by the investigator and then confirmed or overturned by an independent adjudication committee. Secondary endpoints included engraftment, acute GVHD , moderate/severe cGVHD, non-relapse mortality, GVHD and relapse free survival (GRFS), progression free (PFS) and overall survival (OS). The impact of ATLG on immune reconstitution was assessed in 91 patients. Results: Treatment arms were balanced with respect to age, diagnosis, remission status, cytogenetics, graft source (PB or BM), CMV serostatus and conditioning regimen. Median follow up of survivors was 745 days (61, 1425). Regarding the primary endpoint, there was no difference in 2 year moderate/severe cGVHD free survival between ATLG and placebo (48 vs 44%, p = 0.57), nor was there a difference in GRFS (Table 1). Neutrophil engraftment at Day 30 was less in the ATLG arm (85% vs 95%, p=0.00001). Grade 2 or higher infusion reactions were higher in the ATLG arm (16% vs 2.3%, p=0.0001). Reactivation of CMV was similar (27% vs 31%, p=0.58). The Day 180 cumulative incidence of grades 2-4 acute GVHD was lower in the ATLG arm (23 vs 40%, p = 0.003) as was the 2-year cumulative incidence of moderate/severe cGVHD (12 vs 33%, p = 0.000006). However, both 2-year OS and PFS were lower in ATLG treated patients (58 v 76% and 47 vs 67%, respectively) due in part to a higher incidence of relapse (32 vs 19%, p=0.068). Multivariable models confirmed that ATLG was associated with inferior OS, HR 1.85 (1.1-2.9, p=.0075) and PFS, HR 1.63 (1.1-2.41, p=0.015). We then conducted an unplanned post-hoc analysis and discovered a striking influence of conditioning regimen on outcomes. There were no differences in OS or PFS between ATLG and placebo arms in patients receiving Bu/Cy or Bu/Flu but a dramatic difference in patients receiving Cy/TBI conditioning (OS, 88% vs 48% p =0.006 and PFS, 75 vs 29%, p=0.007 in placebo and ATLG arms, respectively). 91 patients (44 ATLG, 47 placebo) participated in the immune reconstitution study. ATLG treatment was associated with lower CD3, CD4, and CD8 counts at Days 30, 100, and 360, respectively. In turn lower CD3, CD4, and CD8 counts assessed as time dependent variables were all associated with inferior OS and PFS as well as higher NRM (data not shown). Conclusion: In this first ever prospective, randomized, double blind trial of ATLG added to tacrolimus /methotrexate in recipients of matched unrelated donor grafts after myeloablative conditioning, there was no significant difference in 2 year moderate/severe cGVHD free survival or GRFS. ATLG did significantly reduce grades 2-4 acute and moderate/severe chronic GVHD. However, overall survival was higher in the placebo arm, driven mainly by patients who received Cy/TBI conditioning. Further analyses are needed to understand the proper role for ATLG in HCT. Disclosures Soiffer: Juno: Membership on an entity's Board of Directors or advisory committees; Kiadis: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Porter:Genentech: Employment; Novartis: Patents & Royalties, Research Funding. Jagasia:Therakos: Consultancy. Szer:Alnylam: Honoraria, Membership on an entity's Board of Directors or advisory committees; Ra Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees. Ritz:Kiadis: Membership on an entity's Board of Directors or advisory committees. Glavin:Neovii Biotech: Employment. Chen:Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding.