Abstract: The approved dose of bosutinib in chronic phase CML is 400 mg QD in first-line and 500 mg QD in later-line treatment. However, given that gastrointestinal (GI) toxicity typically occurs early after treatment initiation, physicians often tend to start therapy with lower doses although this has never been tested systematically in prospective trials in the Western world. The Bo sutinib Do se Optimization (BODO) Study, a multicenter phase II study, investigated the tolerability and efficacy of a step-in dosing concept of bosutinib (starting at 300 mg QD) in chronic phase CML patients in 2 nd or 3 rd line who were intolerant and/or refractory to previous TKI treatment. Of 57 patients included until premature closure of the study due to slow recruitment, 34 (60%) reached the targeted dose level of 500 mg QD following the 2-weekly step-in dosing regimen. While the dosing-in concept failed to reduce GI toxicity (grade II–IV, primary study endpoint) to  〈  40% (overall rate of 60%; 95% CI: 45–74%), bosutinib treatment (mean dosage: 403 mg/day) showed remarkable efficacy with a cumulative major molecular remission (MMR) rate of 79% (95% CI: 66 to 88%) at month 24. Of thirty patients refractory to previous therapy and not in MMR at baseline, 19 (64%) achieved an MMR during treatment. GI toxicity did not significantly impact on patient-reported outcomes (PRO) and led to treatment discontinuation in only one patient. Overall, the results of our trial support the efficacy and safety of bosutinib after failure of second-generation TKI pre-treatment. Trial registration: NCT02577926.

Abstract: Inflammation-induced thrombosis represents a severe complication in patients with myeloproliferative neoplasms (MPN) and in those with kidney dysfunction. Overlapping disease-specific attributes suggest common mechanisms involved in MPN pathogenesis, kidney dysfunction, and thrombosis. Data from 1420 patients with essential thrombocythemia (ET, 33.7%), polycythemia vera (PV, 38.5%), and myelofibrosis (MF, 27.9%) were extracted from the bioregistry of the German Study Group for MPN. The total cohort was subdivided according to the calculated estimated glomerular filtration rate (eGFR, (mL/min/1.73 m2)) into eGFR1 (≥90, 21%), eGFR2 (60–89, 56%), and eGFR3 ( 〈 60, 22%). A total of 29% of the patients had a history of thrombosis. A higher rate of thrombosis and longer MPN duration was observed in eGFR3 than in eGFR2 and eGFR1. Kidney dysfunction occurred earlier in ET than in PV or MF. Multiple logistic regression analysis identified arterial hypertension, MPN treatment, increased uric acid, and lactate dehydrogenase levels as risk factors for kidney dysfunction in MPN patients. Risk factors for thrombosis included arterial hypertension, non-excessive platelet counts, and antithrombotic therapy. The risk factors for kidney dysfunction and thrombosis varied between MPN subtypes. Physicians should be aware of the increased risk for kidney disease in MPN patients, which warrants closer monitoring and, possibly, early thromboprophylaxis.

Abstract: Introduction: Mutations (muts) in JAK2, MPL, and CALR are genetic hallmarks in myeloproliferative neoplasms such as myelofibrosis (MF). Prognostication in MF is predominantly based on clinical parameters according to the Dynamic International Prognostic Scoring System (DIPSS). However, gene mutations become increasingly important allowing for a more precised assessment of prognosis. For instance, CALR mutated MF is associated with favorable prognosis, while mutations in distinct high molecular-risk (HMR) genes are considered adverse. Our multicenter phase-Ib/II MPNSG-0212 trial (NCT01644110) investigating ruxolitinib plus pomalidomide in a total cohort of 92 patients with advanced MF and anemia provides an ideal basis for investigating the genomic landscape and molecular risk in a well-defined study population. Aims & Methods: To assess the genomic landscape in MF patients treated within the MPNSG-0212 trial and to correlate the results with clinical parameters and overall survival (OS). So far, targeted next generation sequencing (NGS) of 269 candidate genes was performed in peripheral blood or bone marrow from 81/92 patients using libraries prepared with SureSelectXT HS (Agilent, Santa Clara, USA). NGS was carried out on a NextSeq550 (Illumina, San Diego, USA). Results: At study entry, median age of the 81 patients was 71 years (range 52-86), median Hb 8.6 g/dL (range 5.4-11.7 g/dl); 30% of patients were RBC transfusion-dependent; 67% had primary MF (PMF) and 33% secondary MF (SMF), respectively. According to DIPSS, the vast majority of the patients were categorized as intermediate-2 (63%) or high-risk (26%) MF; 11% were low- and intermediate-1 risk patients. Overall, 315 muts were identified in 80/81 (99%) patients with a median of 3 muts/patient (range 0-9). Recurrent muts (≥5%) were identified in JAK2 (60%), ASXL1 (30%), SRSF2 (21%), CALR (20%; type-1: 75% [n=12], type-2 and non-type-1/2: 12.5% [n=2] each), MPL (19%), SF3B1 (19%), TET2 (16%), U2AF1 (15%), CBL and EZH2 (10% each), IDH2 and DNMT3A (7% each), PHF6, ZRSR2, and CUX1 (5% each). The majority of the patients (95%) was characterized by the presence of a driver mut in JAK2, CALR, or MPL; 4/81 patients (5%) were triple negative (Figure 1). JAK2mut was associated with TET2mut (p=.047), whereas muts in CALR and TET2 were mutually exclusive (p=.05). CALRmut patients had less co-muts than patients with JAK2/MPL muts (mean 2.5 vs. 4.1, p=.007) and were mutually exclusive with muts in the spliceosome regulating genes SRSF2, SF3B1, U2AF1, and ZRSR2 (p=.009). Compared to MF with mutated JAK2 or MPL, MF patients with mutated CALR had a longer median OS (not reached vs. 3.1 years; p=.04). With regard to high molecular risk (HMR) muts, n=56 were detected in 38 patients (47%), with 40% (15/38) of the patients harboring ≥2 HMR muts. The most commonly mutated HMR genes were ASXL1 (43%; 24/56), followed by SRSF2 (30%), EZH2 (14%), IDH2 (11%), and IDH1 (2%). MPLmut but not JAK2mut or CALRmut were significantly associated with HMR mut (p=.023). HMR mut patients harbored more co-muts than HMR wt patients (median 5 vs. 3; p & lt;.0001). There were no significant differences in the variables age, sex, WBC, Hb, PLT, or LDH level between patients with HMR mut and HMR wt MF. In univariate analysis, patients with HMR mut MF had shorter median OS (2.3 vs 3.7 years, p=.007). In multivariate analysis (HMR mut, age, DIPSS-category, SMF vs. PMF) a higher DIPSS-score (HR, 3.2; 95% CI, 1.5-7.0; p=.004) and muts in HMR genes (HR, 3.5; 95% CI, 1.5-8.1; p=.003) were significant adverse prognostic factors for OS. Conclusions: Our NGS data underline the genomic complexity of advanced MF. CALR mutations were only found in 20% of the patients that were characterized by less co-mutations, mutual exclusivity with spliceosome mutations, and with more favorable outcome suggesting a distinct disease biology. Almost 50% of patients showed mutations in HMR genes which were associated with an inferior OS in univariate and multivariate analyses. §Frank Stegelmann and Konstanze Döhner contributed equally to this work. Figure 1 Figure 1. Disclosures Koschmieder: Shire: Honoraria, Other; Alexion: Other: Travel support; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Geron: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; AOP Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Baxalta: Membership on an entity's Board of Directors or advisory committees, Other; Abbvie: Other: Travel support; CTI: Membership on an entity's Board of Directors or advisory committees, Other; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding; Image Biosciences: Other: Travel support; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karthos: Other: Travel support. Heidel: Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; CTI: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene/BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AOP: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Hochhaus: Bristol-Myers Squibb: Research Funding; Pfizer: Research Funding; Incyte: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Hebart: AbbVie: Honoraria; AstraZeneca: Honoraria; BMS: Honoraria; Janssen: Honoraria; Roche: Honoraria. Isfort: Alexion: Other: Travel reimbursement; Roche: Other: Travel reimbursement; Amgen: Other: Travel reimbursement; Mundipharma: Other: Travel reimbursement; Hexal: Other: Travel reimbursement; BMS: Honoraria; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel reimbursement; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel reimbursement. Reiter: AOP Orphan Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Deciphera: Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses; Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses; Blueprint Medicines: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding. Waller: Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Mylan: Consultancy; Alvotech: Consultancy; Takeda: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees; Lilly: Membership on an entity's Board of Directors or advisory committees, Other: travel support; Chugai: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Other: travel support; Amgen: Membership on an entity's Board of Directors or advisory committees; IPSEN: Other: travel grant. Scheid: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Goethert: Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Travel support; Incyte: Consultancy, Honoraria, Other: Travel support; zr pharma & : Honoraria; BMS: Consultancy, Honoraria, Other: Travel support; AOP Orphan Pharmaceuticals: Honoraria, Other: travel support; Proteros Biostructures: Consultancy. Schafhausen: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Swedish Orphan Biovitrum AB: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Blueprint Medicines: Membership on an entity's Board of Directors or advisory committees. Radsak: Otsuka: Consultancy, Honoraria; Abbvie: Other: e.g. travel support; Astellas: Other: e.g. travel support; TEVA: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: e.g. travel support; Daiichi Sankyo: Consultancy, Honoraria, Other: e.g. travel support; Celgene/BMS: Consultancy, Honoraria, Other: e.g. travel support; Amgen: Other: e.g. travel support; Takeda: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Corat: Consultancy, Honoraria; Cogent Biosciences: Consultancy, Honoraria; JAZZ: Other: e.g. travel support. Gattermann: Takeda: Research Funding; Novartis: Honoraria; Celgene: Honoraria. von Bubnoff: Novartis: Honoraria; Takeda: Honoraria. Brümmendorf: Bristol Myers: Research Funding; Janssen: Honoraria; Novartis: Honoraria, Patents & Royalties, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Repeat Diagnostics: Research Funding; Takepart Media: Honoraria. Döhner: Celgene: Honoraria, Research Funding; Agios: Honoraria, Research Funding; GEMoaB: Honoraria; Astex Pharmaceuticals: Honoraria; Astellas: Honoraria, Research Funding; Oxford Biomedica: Honoraria; Novartis: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding; Janssen: Honoraria; Helsinn: Honoraria; Gilead: Honoraria; AstraZeneca: Honoraria; Abbvie: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Berlin-Chemie: Honoraria; Roche: Honoraria; Pfizer: Research Funding. Griesshammer: Amgen: Consultancy, Honoraria; AOP Orphan: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; CTI: Consultancy, Honoraria; Shire: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria. Stegelmann: BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Döhner: Abbvie: Consultancy, Honoraria; Janssen: Honoraria, Other: Advisory Board; Jazz Roche: Consultancy, Honoraria; Daiichi Sankyo: Honoraria, Other: Advisory Board; Astellas: Research Funding; Celgene/BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Agios and Astex: Research Funding. OffLabel Disclosure: Pomalidomide was shown to be active in patients with myelofibrosis in particular in the treatment of anemia (Tefferi et al 2009, Begna et al 2011, Mesa et al 2010)

Abstract: Introduction: Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) characterized by expansion of the granulocytic, erythrocytic, and megakaryocytic lineages in the bone marrow and peripheral blood, and in most cases, by the presence of a JAK2 mutation. Survival of patients with PV is decreased compared with age-matched controls, and this is mainly due to thromboembolic complications followed by progression to post-PV myelofibrosis and acute leukemia. While no curative treatment exists, cytoreductive treatment with hydroxyurea (HU) or ropeginterferon is approved in EU for first-line therapy, and ruxolitinib (RUX) is approved in EU and US for second-line therapy in patients with HU intolerance or resistance. The current futility analysis assesses the efficacy of ruxolitinib in newly-diagnosed PV treated within the Ruxo-BEAT trial. Methods: This clinical trial entitled "Ruxolitinib versus Best Available Therapy in patients with high-risk Polycythemia Vera or high-risk Essential Thrombocythemia" (Ruxo-BEAT; NCT02577926) is a multicenter, open-label, two-arm phase-IIb trial with a target population of 380 pts with PV and ET. Patients in first-line PV and in first and later lines ET are randomized in a 1:1 manner to receive either RUX or best available therapy (BAT). Crossover from BAT to RUX is possible in eligible patients after 6 months. Patients with PV in the RUX arm receive a starting dose of 10 mg bid and may increase their dose up to 20 mg bid. Primary endpoint is the rate of complete clinicohematologic response rate (CHR) at month 6 as defined by Barosi et al Blood 2009. Secondary endpoints include differences in the absence of phlebotomies, spleen size, patient-reported outcomes, and survival. This is a pre-specified futility analysis of RUX in the PV arm, after 50 PV patients had been enrolled. Of the 50 patients, 28 patients with newly-diagnosed PV were randomized into the RUX arm and were analyzed (a maximum of 6 weeks of HU, anagrelide, or interferon therapy was allowed). The PV arm would have to be closed if no favorable trend were observed for RUX for any of the following variables: (1) improvement (decrease) in the hematocrit level during 6 months of treatment, (2) improvement (decrease) of the JAK2V617F allele burden during 6 months of treatment, or (3) improvement of one of the following three symptom variables assessed by physician´s judgement or via MPN Symptom Assessment Form (MPN-SAF) during 6 months of treatment: pruritus, night sweats, or bone pain. Differences between screening (Hct) or baseline (all other variables) and end of month 6 (all variables) were calculated using Fisher´s exact test (for physician-assessed pruritus and night sweats) or the Wilcoxon matched-pairs signed rank test (all other variables). Results: 28 patients received RUX for at least 6 months. After 6 months, the mean hematocrit level decreased from 45.9+/-5.6% to 41.0+/-5.0% (mean+/-SD) (p=0.0003). The number of phlebotomies calculated per year decreased from 4.2+/-3.9% to 0.96+/-2.1 (p=0.0009). Mean JAK2V617F allele burden decreased from 50.2+/28.4% to 44.0+/-28.5% (p=0.0039). The percentage of patients, as assessed by the physician, with pruritus or night sweats decreased from 41% to 26% (trending with p=0.13), and from 30% to 11% (p=0.02), respectively. The points reported by patients themselves on the MPN-SAF survey for pruritus decreased from 2.7+/-3.0 to 1.3+/-1.5 (p=0.0095) and there was a strong trend for reduction of night sweat points (from 3.1+/-3.6 to 1.6+/-2.4; p=0.0579), while the points for bone pain remained unaltered (2.0+/-2.8 to 1.4+/-2.2; p=0.215). Conclusion: Treatment with ruxolitinib in first line PV is efficient regarding the above-mentioned endpoints. Recruitment of our trial will be ongoing. In order not to weaken the study´s statistical power, comparison of both arms was not performed. Disclosures Koschmieder: Ariad: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers-Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Shire: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis Foundation: Research Funding; CTI: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AOP Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Isfort:Mundipharma: Other: Travel reimbursement; Amgen: Other: Travel reimbursement; Hexal: Other: Travel reimbursement; BMS: Honoraria; Ariad: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Other: Travel reimbursement; Novartis: Consultancy, Honoraria, Other: Travel reimbursement; Roche: Other: Travel reimbursement; Alexion: Other: Travel reimbursement. Schafhausen:Novartis: Consultancy, Honoraria; Incyte: Consultancy, Equity Ownership, Honoraria. Griesshammer:Novartis: Consultancy, Honoraria, Speakers Bureau. Platzbecker:Abbvie: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Döhner:CTI Biopharma: Consultancy, Honoraria; Daiichi: Honoraria; Jazz: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Janssen: Honoraria. Jost:Abbvie: Consultancy, Patents & Royalties: Royalty payments for the drug compound ABT-199, Research Funding; Bohringer: Consultancy, Research Funding; BMS: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Celgene: Other: Travel Support; Novartis: Research Funding. von Bubnoff:Novartis: Research Funding. Stegelmann:Novartis: Consultancy, Honoraria; Incyte: Consultancy, Honoraria. Crysandt:Amgem: Other: travel grant; celgene: Other: travel grant; Pfizer: Other: travel grant; Gilead: Other: travel grant; Incyte: Membership on an entity's Board of Directors or advisory committees. Gezer:AMGEM: Membership on an entity's Board of Directors or advisory committees. Brümmendorf:Merck: Consultancy; Pfizer: Consultancy, Research Funding; University Hospital of the RWTH Aachen: Employment; Janssen: Consultancy; Ariad: Consultancy; Novartis: Consultancy, Research Funding. OffLabel Disclosure: Ruxolitinib as first-line treatment in newly-diagnosed PV

Abstract: Patients (pts) with polycythemia vera (PV) suffer from pruritus, night sweats, and other symptoms, as well as from thromboembolic complications and progression to post-PV myelofibrosis. Ruxolitinib (RUX) is approved for second-line therapy in high-risk PV pts with hydroxyurea intolerance or resistance. The RuxoBEAT trial (NCT02577926, registered on October 1, 2015, at clinicaltrials.gov) is a multicenter, open-label, two-arm phase-IIb trial with a target population of 380 pts with PV or ET, randomized to receive RUX or best available therapy. This pre-specified futility analysis assesses the early clinical benefit and tolerability of RUX in previously untreated PV pts (6-week cytoreduction was allowed). Twenty-eight patients were randomly assigned to receive RUX. Compared to baseline, after 6 months of treatment, there was a significant reduction of median hematocrit (46 to 41%), the median number of phlebotomies per year (4.0 to 0), and median patient-reported pruritus scores (2 to 1), and a trend for reduced night sweat scores (1.5 to 0). JAK2V617F allele burden, as part of the scientific research program, also significantly decreased. One hundred nine adverse events (AEs) occurred in 24/28 patients (all grade 1 to 3), and no pt permanently discontinued treatment because of AEs. Thus, treatment with ruxolitinib in untreated PV pts is feasible, well-tolerated, and efficient regarding the above-mentioned endpoints.

Abstract: Introduction: Ph-negative myeloproliferative neoplasms (MPN) represent a heterogeneous group of hematological malignancies which differ in various aspects such as clinical manifestation, underlying genetic aberrations, cytomorphological features and life expectancy. However, across all subtypes, patients (pts) with MPN often suffer from severe symptoms, resulting in an impairment of the quality of life (QoL). Methods: The German Study Group for MPN (GSG-MPN) Bioregistry is a non-interventional prospective study including pts of at least 18 years with diagnosis of Ph-negative MPN according to WHO criteria (2008) having provided written informed consent. The Bioregistry study also includes assessment of QoL at baseline and on an annual basis, with all pts completing the standardized MPN-SAF-TSS questionnaire (German version) and an additional item indicating pts' subjective overall QoL on an 11-point Likert scale. Total scores range from 0 to 90 and were calculated if at least 6 items were answered (Emanuel RM et al., J Clin Oncol. 2012; 30 (33): 4098-103.)). Clinical variables, as documented in the registry, included comorbidities, reported symptoms as assessed by the physician, bleeding, and thromboembolic events (TEE). For statistical analysis, standard descriptive methods, Spearman correlation coefficient, Wilcoxon test/Kruskal-Wallis test for significance testing, and Kendall´s tau-b statistics were used. Results: 1,403 pts who had completed at least six items of the QoL assessment at baseline were included in this analysis. Median age at diagnosis was 58 years (interquartile range [IQR] 22), 98% were Caucasian, 50% were female. 494 pts were diagnosed with essential thrombocythemia (ET, 35%), 444 pts with polycythemia vera (PV, 32%), 302 pts with primary myelofibrosis (PMF, 22%), 83 pts with MPN-unclassifiable (MPNu, 6%), 43 pts with post-ET-myelofibrosis (pET-MF, 3%) and 37 pts with post-PV-myelofibrosis (pPV-MF, 3%). The most common complaint reported via the MPN-SAF-TSS was fatigue, occurring in more than 80% of the pts in all entities except MPNu (77%). More than 50 % of pts in each entity reported to suffer from early satiety, night sweats, concentration problems, or overall impairment of QoL. Table 1 summarizes all 9 symptoms and overall QoL from the questionnaire categorized by entity. Interestingly, the pts suffering from PET-MF reported the highest symptom burden, while PPV-MF pts showed the lowest overall symptom burden (median total QoL score of 23 vs. 16; p=0.01). The strongest correlations among the different symptoms were seen for fatigue and overall QoL (Spearman´s rho 0.57, p 〈 0.001) as well as concentration problems and overall QoL (Spearman´s rho 0.33, p 〈 0.001). Furthermore, the impact of variables such as age, comorbidities and TEE on QoL was assessed. Abdominal discomfort increased with age (rho = -0.14, p 〈 0.001). A history of TEE before baseline assessment correlated significantly with fatigue scores (Spearman rho= 0.07, p 〈 0.01) and with concentration problems (rho=0.07, p 〈 0.01). With an increasing number of TEE, scores for both of these items worsened over time (p 〈 0.01, respectively). Moreover, MPN-total score (MPN-TSS) was higher in pts with more comorbidities (Median: 18 (IQR:23), and 25 (27) for pts with 〈 3 versus ≥3 comorbidities, respectively, p= 0.017). Next, we compared data on 5 of the pts symptoms (reported in the questionnaire) to their assessment by the treating physician (only 5 items were available both in the questionnaire and in our registry database) in order to understand whether the "physician´s opinion" is congruent with the patient´s reported outcome in the questionnaire. While there were clear associations between the two data sources, there were also significant discrepancies, e.g., the physician did not indicate fatigue in about 20% of pts with self-assessed fatigue score of 〉 =6 points. The most concordant symptom was night sweats (further details in table 2). Conclusions: Most MPN pts suffer from a significant symptom burden which impairs their QoL. TEE influence fatigue and concentration problems. The perception of symptoms (particularly with respect to fatigue) differs between pts and treating physician which suggests that questionnaires should be used on a routine basis in order to faithfully reflect patient´s degree of suffering from MPN and/or treatment. Disclosures Isfort: Amgen: Other: i.e. travel support; Mundipharma: Other: i.e. travel support; Roche: Other: i.e. travel support; Incyte/Ariad: Consultancy; Pfizer: Consultancy, Honoraria, Other: i.e. travel support; BMS: Honoraria; Novartis: Consultancy, Honoraria, Other: i.e. travel support; Alexion: Other: i.e. travel support; Hexal: Other: i.e. travel support. Stegelmann:Novartis: Consultancy, Honoraria. Al-Ali:Gilead: Consultancy, Research Funding; Otsuka: Consultancy, Honoraria; Alexion: Honoraria; Novartis: Consultancy, Honoraria, Other: Travel support, Research Funding; Celgene: Honoraria, Other: Travel support, Research Funding. Goethert:BMS: Consultancy, Honoraria, Other: i.e. travel support; Incyte: Consultancy, Honoraria, Other: i.e. travel support; Pfizer: Consultancy, Honoraria; Novartis: Honoraria; Proteros Biostructures: Honoraria; AOP Orphan: Other: i.e. travel support. Haenel:Novartis: Honoraria; Takeda: Honoraria; Roche: Honoraria; Amgen: Honoraria. Platzbecker:Celgene: Research Funding. Griesshammer:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Brümmendorf:Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Janssen: Consultancy; Merck: Consultancy; Takeda: Consultancy.