Myeloproliferative Neoplasm Symptom Assessment Form Research Articles

Unmet Needs for Symptom Control in Essential Thrombocythemia with Front Line Therapy

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

Assessment and Validation of the EQ-5D Among a Population of Myeloproliferative Neoplasm Patients

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

Symptom Burden Profile in Myelofibrosis Patients with Thrombocytopenia: Lessons and Unmet Needs

BackgroundMyelofibrosis (MF) is a clonal myeloproliferative neoplasm (MPN) associated with a high degree of symptomatology, progressive cytopenias and potential to transform into acute myelogenous leukemia (AML). Thrombocytopenia amongst MF patients is a proven negative prognostic indicator and predictor of transformation to AML. Ruxolitinib is an effective JAK inhibitor for MF symptoms and splenomegaly, but is not indicated in patients with severe thrombocytopenia. Phase III trials of pacritinib have shown alleviation of the MF symptom burden amongst patients with thrombocytopenia (ASCO 2015 Mesa et. al.). In this study, we assessed the symptom burden of MF patients with significant thrombocytopenia who were naïve to pacritinib.MethodsData was assessed from a prospectively collected international database of MF patients in which demographics, disease features, and MF symptoms utilizing the myeloproliferative neoplasm symptom assessment form (MPN-SAF; Scherber et al, 2011). The MPN-SAF includes the patient's perceptions of common MPN-related symptoms and overall quality of life (QOL) on a 0 (absent) to 10 (worst imaginable) scale. Total symptom score (TSS) was computed based on symptom items using the published scoring algorithm on a 0 (all reported symptoms absent) to 100 (all reported symptoms worst imaginable) scale. MF risk scores were calculated using the DIPSS criteria (Gangat, 2011). Thrombocytopenia was defined as a platelet count <100 x 10(9)/L, anemia was defined as hemoglobin<10 g/dL and leukopenia was defined as a white blood cell count <4.0 x 10(9)/L. Associations between the MPN-SAF individual symptoms were investigated using Pearson correlations.ResultsDemographic and Disease Features:A total of 418 patients with (n=89) and without (n=329) thrombocytopenia completed the MPN-SAF. Patients with thrombocytopenia were slightly younger (57.4 vs. 61.0, p=0.01) with longer disease durations (11.9 years vs. 8.8 years, p=0.0489) and had a higher prevalence of primary myelofibrosis (PMF; 82% vs. 66%, p=0.01). The presence of thrombocytopenia was associated with other laboratory abnormalities including anemia (60.7% vs. 25.3%, p<0.001) and leukopenia (34.8% vs. 52.3%, p<0.001), along with the need for red blood cell transfusions (34.8% vs. 14.6%, p<0.001). Patient cohorts did not differ by gender, DIPSS risk score, history of prior thrombosis or hemorrhage. In comparing patients with severe thrombocytopenia (<50 x 10(9)/L, n=43) to those with moderate thrombocytopenia (51-100 x 10(9)/L, n=46), severe thrombocytopenia patients were more likely to have anemia (74.4% vs. 47.8%, p=0.01) and require red blood cell transfusions (51.2% vs. 19.6%, p=0.002).SymptomsScores for individual MPN-SAF items were assessed for each subgroup. Patients with thrombocytopenia had markedly higher total symptom scores than patients without thrombocytopenia (32.8 vs. 24.1, p<0.001). Individual scores were also higher for most items (fatigue, early satiety, inactivity, dizziness, sad mood, sexuality, cough, night sweats, itching, fever, weight loss, overall QOL)[Figure 1]. No significant differences in MPN SAF TSS or individual symptom scores were observed in comparing severe vs. moderate thrombocytopenia patients.DiscussionMF patients with thrombocytopenia have distinctive clinical characteristics and face a significantly more severe symptom burden. Importantly, despite thrombocytopenia being a recognized risk factor for disease advancement, no correlations are noted between patient symptomatology and risk category. In addition, patients with severe thrombocytopenia do not differ symptomatically from patients with moderate thrombocytopenia despite having more severe anemia, leukopenia and transfusion requirements. This implies that the degree of symptomatology expressed by thrombocytopenic MF patients occurs independent from the exact platelet value.ConclusionThe results of this study suggest that patients with thrombocytopenia will benefit from aggressive symptomatic control, potentially from targeted agents. [Display omitted] DisclosuresKiladjian:Novartis: Consultancy; Novartis: Other: Travel grant; Research Funding paid to institution (Hôpital Saint-Louis et Université Paris Diderot); Incyte Corporation: Consultancy. Zweegman:Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Harrison:Shire: Speakers Bureau; CTI Biopharma: Consultancy, Honoraria, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau; Gilead: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau. Cervantes:Novartis: Consultancy, Speakers Bureau; Sanofi-Aventis: Consultancy; CTI-Baxter: Consultancy, Speakers Bureau. Barbui:Novartis: Speakers Bureau. Etienne:ARIAD: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: Congress Travel/Accomodations, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau. Roy:BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Vannucchi:Shire: Speakers Bureau; Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Baxalta: Membership on an entity's Board of Directors or advisory committees. Mesa:Novartis. Research- incyte, Gilead, cti, Genentech, promedior, NS Pharma: Consultancy.

A Phase 2 Study to Evaluate the Efficacy and Safety of Simtuzumab in Adult Subjects with Primary, Post Polycythemia Vera (PV) or Post Essential Thrombocythemia (ET) Myelofibrosis

Background: Simtuzumab (SIM) is a humanized monoclonal antibody that inhibits lysyl oxidase-like molecule 2 (LOXL2), an extracellular matrix enzyme that catalyzes the covalent cross-linking of collagen and is widely expressed across many fibrotic diseases. In pre-clinical models, inhibition of LOXL2 blocks fibroblast activation, which plays an important role in the development of organ fibrosis. In Phase 1 studies, SIM was well-tolerated in patients (pts) with advanced solid tumors, liver fibrosis, and idiopathic pulmonary fibrosis (IPF). A Phase 2, open-label study to determine the efficacy of SIM alone (Stage 1) and combined with ruxolitinib (rux) (Stage 2) in pts with primary myelofibrosis (PMF) and post-ET/PV MF was initiated.Methods: Eligible pts had intermediate-1, intermediate-2, or high risk disease and Eastern Cooperative Oncology Group performance status of <2. The primary endpoint was rate of clinical response as defined by a reduction in bone marrow fibrosis score following 24 weeks of treatment with SIM. Patients were randomized in a 1:1 ratio to receive 200 mg or 700 mg SIM by intravenous infusion every 2 weeks as monotherapy (Stage 1, n=24) or combined with rux (Stage 2, n=30). Patients received SIM for up to 24 weeks. Bone marrow biopsies and aspirates were performed approximately every 3 months. Bone marrow fibrosis scoring was performed and quantified at local investigator sites using the European Consensus on Grading Bone Marrow Fibrosis. Myelofibrosis symptoms were evaluated using the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) and changes in hematologic parameters and splenomegaly were assessed.Results: Between 7/14/11 and 9/22/14, 54 pts were randomized and treated (200 mg SIM [n=12], 700 mg SIM [n=12], 200 mg SIM/rux [n=15], and 700 mg SIM/rux [n=15]). In Stage 1, 0 subjects (0%) in the SIM 200 mg group and 2 subjects (16.7%; 90% CI 3.0%, 43.8%) in the SIM 700 mg group showed a reduction in bone marrow fibrosis score from Baseline to Week 24. In Stage 2, 1 subject (6.7%; 90% CI 0.3%, 27.9%) in the SIM 200 mg/rux group and 2 subjects (13.3%, 90% CI 2.4%, 36.3%) in the SIM 700 mg/rux group showed a reduction in bone marrow fibrosis score from Baseline to Week 24. In an exploratory analysis, similar numbers of subjects showed increases in bone marrow fibrosis scores. SIM treatment was not associated with meaningful improvements in hematologic parameters or reductions in MPN-SAF score or spleen size. The most frequent adverse events were those commonly associated with MF, including constitutional symptoms and reductions in hematological parameters.Conclusions: SIM treatment alone or in combination with rux is safe but does not reliably reduce bone marrow fibrosis in pts with MF. The reason for reduction of marrow fibrosis in some patients and increase in others is unclear and may be sampling variability. Clinical studies of SIM in IPF and liver fibrosis are ongoing. DisclosuresSavona:Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Research Funding; Astex Pharmaceuticals, Inc: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Mesa:Incyte Corporation: Research Funding; CTI Biopharma: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Pfizer: Research Funding; Promedior: Research Funding; Genentech: Research Funding; NS Pharma: Research Funding; Gilead: Research Funding. Oh:CTI Biopharma: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. Dong:Gilead Sciences: Consultancy, Equity Ownership. Thai:Gilead Sciences: Employment, Equity Ownership. Gotlib:Allakos, Inc.: Consultancy.

Disease and Clinical Characteristics of Patients with Polycythemia Vera: An Early View of the Reveal Study

Background: Patients with polycythemia vera (PV) have an increased symptom burden (eg, fatigue, pruritus, and splenomegaly-related symptoms) and an increased risk of mortality compared with the general population, often resulting from thrombotic events, disease transformation to myelofibrosis, or secondary malignancies. There are limited data regarding PV burden and treatment patterns in a contemporary, real-world US setting. REVEAL is an ongoing observational study being conducted to describe contemporary demographics, burden of disease, clinical management, patient-reported outcomes, and healthcare resource utilization among patients with PV in the US. The objective of this assessment is to describe the clinical characteristics at enrollment among patients currently enrolled in REVEAL (enrollment from July 22, 2014 to June 9, 2015).Methods: REVEAL is a multicenter, noninterventional, nonrandomized, prospective, observational study. Eligible patients are ≥18 years of age with a PV diagnosis and currently under active management by a physician in the US. Data regarding disease and clinical characteristics, patient-reported outcomes, and health resource utilization are being collected at usual-care visits over a planned 36-month observation period. Analyses of these preliminary data were descriptive.Results: At data cutoff, 865 patients were enrolled (total planned enrollment, n=2000) from 174 sites (academic, n=27; community, n=147). Median (range) age at enrollment was 67 (22-95) years, 55.5% were male, 89.5% were white, and 45.4% had a history of smoking. Most patients (99.4%) had health insurance, including Medicare (56.0%), PPO (24.3%), or HMO (11.6%). Fifty-two percent were retired, 29.6% were employed, and 4.5% were unable to work or disabled. A total of 40.2% of patients completed a college/graduate degree, 19.9% had some college, and 32.5% completed high school or the equivalent.Documented major World Health Organization diagnostic criteria included JAK2V617F mutation in 50.9% of patients, elevated hemoglobin in 52.3%, and red cell mass in 5.5%. A bone marrow biopsy was conducted in 24.0% of patients, approximately half of whom (52.4% of the 24.0%) had trilineage myeloproliferation. Erythropoietin levels were abnormal in 19.7% of patients. Approximately half (46.6%) of patients had physician-reported PV-related symptoms at diagnosis, most frequently fatigue (25.2%) and pruritus (14.0%).At enrollment, median disease duration was 52.6 months; 42.3% of patients were diagnosed ≥5 years before enrollment. The most common comorbidities were hypertension (51.3%), obesity (14.2%), dyspnea (13.4%), myalgia (11.2%), and diabetes mellitus (11.1%). Mean hematocrit was 44.9%, hemoglobin was 14.5 g/dL, white blood cell count was 11.4×109/L, platelet count was 363.7×109/L, and absolute neutrophil count was 363.7×109/L. Twenty-one percent of patients had a history of thrombotic events, with 13.1% and 8.6% of patients experiencing ≥1 venous or arterial thromboembolic event, respectively. Of the 261 reported thrombotic events, 43.7% occurred after diagnosis of PV. The most common PV symptoms recorded at enrollment (using the Myeloproliferative Neoplasm Symptom Assessment Form) were fatigue (37.1%), pruritus (24.0%), headache (18.6%), insomnia (17.0%), dizziness (13.2%), bone pain (10.5%), and blurred vision (7.9%); 19.7% of 518 evaluable patients had palpable splenomegaly. Fewer than half of patients were receiving aspirin at enrollment (47.7%). The most common PV treatments ± aspirin were phlebotomy (PBT; 63.5%), hydroxyurea (HU; 42.2%), watchful waiting (5.3%), and ruxolitinib (3.1%); 23.0% of patients received PBT + HU.Conclusion: The REVEAL study is unique in that it captures data from both academic and community centers, and therefore includes a broader segment of the PV population typically not described in the literature. REVEAL can provide novel insights into questions related to the contemporary demographics of PV, practice patterns regarding diagnosis and therapy, and the real-world burden of PV and its impact on patients' quality of life and work productivity. Preliminary descriptive data from this early subset of patients suggest that a high proportion of patients report having PV-related symptoms at diagnosis, fewer patients are treated with aspirin than expected, and that thromboembolic event rates remain high after diagnosis. DisclosuresStein:Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees. Moliterno:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Boccia:Incyte Corporation: Honoraria. Naim:Incyte Corporation: Employment, Equity Ownership. Cordaro:Incyte Corporation: Employment, Equity Ownership. Peng:Incyte Corporation: Employment, Equity Ownership. Sun:Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Mesa:Promedior: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; NS Pharma: Research Funding; CTI Biopharma: Research Funding; Gilead: Research Funding; Pfizer: Research Funding; Incyte Corporation: Research Funding; Genentech: Research Funding.

Impact of Disease Duration upon Symptom Burden Amongst Patients with Myeloproliferative Neoplasms (MPNs)

Background: The Philadelphia chromosome negative myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF) all have a time dependent risk of progression to either an advanced myelofibrotic state (post ET/PV MF) and/or to acute myeloid leukemia. The impact of disease duration upon the MPN symptom burden is not well understood, nor are the precise mechanisms of disease progression. We sought to better understand the impact of disease duration on MPN symptom burden.Methods:Symptom burden data was collected utilizing the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) amongst MPN patients, collected at the time of an office visit in an international cohort of MPN patients as previously described (Scherber et. al.). Symptom burden assessment was a previously validated 27-item symptom burden questionnaire scored on a 0-10 scale (0= as good as it can be, 10 = as bad as it could be). The patient or provider was asked to report the time since MPN diagnosis. MPN duration was determined to be early if the diagnosis was established between 0 to 5 years ago, intermediate if the diagnosis was established between 6 to 10 years ago, and late if the diagnosis was established 11 years ago or more. Anemia was defined as a red blood cell count less than 10 g/dL, leukopenia was defined as a white blood cell count was below 4 x 109, and thrombocytopenia if the platelet count was below 150 x109. Statistical significance was calculated using ANOVA f-test and chi squared.Results:Patient demographics and disease burden: A total of 1443 patients responded to the survey, including 592 (41%) ET, 549 (38%) PV, and 302 (21%) MF patients, including 181 (60%) primary MF, 67 (22%) post-ET MF, and 54 (18%) post-PV MF. Among MF patients, mean duration of MPN diagnosis was 9 years, and mean duration MF diagnosis was 4.7 years. Among respondents, 757 fit criteria for early disease duration, 353 fit criteria for intermediate disease duration, and 333 fit criteria for late disease duration. Respondent mean age was 62 years and approximately half of respondents were female (55%). Patients with longer diagnosis duration tended to be older (p=0.009) and were most likely to have anemia (0.02), leukopenia (p=0.01), or thrombocytopenia (p=0.03). These individuals were also most likely to have a history of hemorrhage (p=0.007) or require red blood cell transfusions (p<0.001).Combined cohort symptom burden: On average among the combined cohort of ET, PV and MF patients, symptoms tended to worsen with time with this effect being significant for symptom items of fatigue (BFI, p<0.04), concentration (p=0.007), insomnia (p=0.02), sexual difficulties (p=0.002), cough (p=0.03), night sweats (p=0.002), and pruritus (p=0.02). Symptoms of early satiety (p=0.004), concentration difficulties (p=0.01), insomnia (p=0.03), sexual difficulties (p=0.02), cough (p=0.01), and night sweats (p=<0.001) had significantly higher prevalence in those with longer disease duration. Similarly, the total calculated MPN-10 score (p=0.008) and quality of life assessment (0.03) demonstrated worsened outcomes with time (Table 1). No significant differences in symptoms for the combined cohort were observed among individuals diagnosed 0 to 1 years ago compared to those with a diagnosis established between 2 and 5 years ago.Symptom burden in MPN subtypes. When evaluating specific MPN types, patients with essential thrombocythemia experienced significantly greater sexual difficulties over time (p=0.03). The severity (p=0.01) and incidence (p=0.03) of pruritus and incidence of night sweats (p<0.001) were significantly increased over time for individuals with PV. For those with MF, the severity (p= 0.01) and incidence (p=0.009) of cough also significantly increased with longer diagnosis duration.DiscussionOverall, significant worsening in symptom burden can be recognized over time for individuals diagnosed with MPNs. Diagnosis may not necessarily correlate with disease duration as the timing of diagnosis may be delayed from onset of disease. Given the intent of this abstract to evaluate changes with disease duration, we did not investigate correlations between symptom burden and cytopenias. We do know that risk factors for survival in the MPNs include older age and thrombosis, however, disease duration should be investigated as an alternative marker of burden in future survival studies. [Display omitted] DisclosuresHarrison:CTI Biopharma: Consultancy, Honoraria, Speakers Bureau; Shire: Speakers Bureau; Gilead: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau. Kiladjian:Incyte Corporation: Consultancy; Novartis: Other: Travel grant; Research Funding paid to institution (Hôpital Saint-Louis et Université Paris Diderot); Novartis: Consultancy. Zweegman:Celgene: Research Funding; Janssen: Research Funding; Takeda: Research Funding. Barbui:Novartis: Speakers Bureau. Etienne:Novartis: Consultancy, Honoraria, Other: Congress Travel/Accomodations, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; ARIAD: Consultancy, Honoraria, Speakers Bureau. te Boekhorst:CTI Biopharma: Consultancy; Novartis: Consultancy. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Other: Research Funding paid to institution (University of Florence), Research Funding; Shire: Speakers Bureau; Baxalta: Membership on an entity's Board of Directors or advisory committees. Mesa:Novartis. Research- incyte, Gilead, cti, Genentech, promedior, NS Pharma: Consultancy.

Analysis of Outcomes By Patient Subgroups in Patients with Myelofibrosis Treated with Pacritinib Vs Best Available Therapy (BAT) in the Phase III Persist-1 Trial

Introduction: There are few effective treatment options available for patients (pts) with myelofibrosis (MF). Pts with thrombocytopenia, a risk factor for shorter overall survival, have poorer prognosis (Gangat, J Clin Oncol 2010). Pacritinib is a kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CFSR1 and has demonstrated minimal myelosuppression in clinical trials (Hart, Leukemia 2011; Komrokji, Blood 2015; Mesa, ASCO 2015). In the phase III open-label PERSIST-1 trial, a significantly greater proportion of pts treated with pacritinib achieved spleen volume reductions (SVR) ≥35% vs BAT (ITT: 19.1% vs 4.7%, p=0.0003; pts evaluable at baseline and Week 24: 25.0% vs 5.9%, p=0.0001; Mesa, ASCO 2015). This analysis examines pt responses across subgroups.Methods: Pts naive to treatment with JAK inhibitors were randomized 2:1 to receive oral pacritinib 400 mg once daily or BAT. Stratification factors included DIPSS risk status and baseline platelet count. Pts were eligible who had DIPSS Intermediate (Int)-1, Int-2, or High risk disease; absolute neutrophil count >500/µL; palpable splenomegaly ≥5 cm; and baseline Total Symptom Score (TSS) ≥13 using the Modified MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS and TSS 2.0). There was no restriction on baseline platelets or hemoglobin (Hgb) levels. The primary endpoint was the proportion of pts achieving SVR ≥35% at Week 24 by centrally-reviewed MRI or CT and the secondary endpoint was the proportion of pts achieving ≥50% reduction in TSS from baseline at Week 24 using 6 symptoms from the MPN-SAF TSS. Pt responses were analyzed by baseline risk factors for MF including platelet counts (<50,000/µL vs ≥ 50,000/µL and <100,000/µL vs ≥100,000/µL), sex, age (≥65 y vs <65 y), JAK2V617F mutation status (positive vs negative), baseline MF diagnosis (primary MF [PMF] vs secondary MF), reticulin and collagen fibrosis staging (> 1 vs ≤1), TSS (≥20 vs <20), white blood cell count (>25×109/L vs ≤25×109/L), peripheral blasts (≥5% vs <5%), Hgb (<10 g/dL vs ≥10 g/dL), transfusion dependency by Gale criteria (Y vs N), time from diagnosis (<12 mos vs ≥12 mos), ECOG PS (2-3 vs 0-1), and bone pain (>3 vs ≤3). In multivariate logistic regressions, the odds of SVR ≥35% and TSS reduction ≥50% at Week 24 were modeled as a function of prognostic factors for MF and adjusted for treatment (pacritinib vs BAT). Results for the 6 symptoms common to both TSS versions are reported.Results: 327 pts were enrolled and randomized (pacritinib: 220, BAT: 107). Overall, 62% of pts had PMF; 32% had baseline platelets <100,000/µL and 16% had <50,000/µL; 75% were positive for JAK2V617F. After a median follow-up of 8.4 months, treatment with pacritinib resulted in consistent rates of SVR across subgroups (Figure 1). When comparing vs BAT, the greatest differences in SVR ≥35% rates between treatment arms were observed in pts with baseline platelets <50,000/μL (+22.9% vs BAT), JAK2V617F-negative pts (+23.0% vs BAT) and those aged <65 y (+21.2% vs BAT). Improvements in TSS (TSS and TSS 2.0 reduction ≥50%) were also consistent for pts receiving pacritinib (Figure 2). By multivariate analysis, SVR ≥35% was significantly correlated only with ECOG PS ≥2 (odds ratio [OR]=2.97, p=0.030) and TSS reduction ≥50% was significantly correlated only with bone pain >3 (OR=0.35, p=0.004).Conclusions: Treatment with pacritinib resulted in consistent rates of SVR ≥35% and TSS reduction ≥50% irrespective of baseline characteristics. Comparisons vs BAT were favorable for all patient subpopulations examined for both endpoints. These results support the use of pacritinib across all intermediate- or high risk MF pt subgroups analyzed. [Display omitted] [Display omitted] DisclosuresVannucchi:Shire: Speakers Bureau; Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Baxalta: Membership on an entity's Board of Directors or advisory committees. Off Label Use: This abstract discusses off-label use of pacritinib. Mesa:Gilead: Research Funding; NS Pharma: Research Funding; Incyte Corporation: Research Funding; Genentech: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Promedior: Research Funding; Pfizer: Research Funding; CTI Biopharma: Research Funding. Cervantes:Novartis: Consultancy, Speakers Bureau; Sanofi-Aventis: Consultancy; CTI-Baxter: Consultancy, Speakers Bureau. Prasad:BIOGEN IDEC: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Speakers Bureau. Elinder:Celgene: Consultancy. Recher:Sunesis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Chugai: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. te Boekhorst:CTI Biopharma: Consultancy; Novartis: Consultancy. Somervaille:Novartis Pharmaceuticals Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees. Dean:CTI Biopharma: Employment, Equity Ownership. Harrison:Shire: Speakers Bureau; Gilead: Honoraria; CTI Biopharma: Consultancy, Honoraria, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau.

A new internet-based tool for reporting and analysing patient-reported outcomes and the feasibility of repeated data collection from patients with myeloproliferative neoplasms.

An Internet-based tool for reporting and analysing patient-reported outcomes (PROs) has been developed. The tool enables merging PROs with blood test results and allows for computation of treatment responses. Data may be visualized by graphical analysis and may be exported for downstream statistical processing. The aim of this study was to investigate, whether patients with myeloproliferative neoplasms (MPNs) were willing and able to use the tool and fill out questionnaires regularly. Participants were recruited from the outpatient clinic at the Department of Haematology, Roskilde University Hospital, Denmark. Validated questionnaires that were used were European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, Myeloproliferative Neoplasm Symptom Assessment Form, Brief Fatigue Inventory and Short Form 36 Health Survey. Questionnaires were filled out ≥ 6 months online or on paper according to participant preference. Regularity of questionnaire submission was investigated, and participant acceptance was evaluated by focus-group interviews. Of 135 invited patients, 118 (87 %) accepted participation. One hundred and seven participants (91 %) preferred to use the Internet-based tool. Of the 118 enrolled participants, 104 (88 %) submitted PROs regularly ≥ 6 months. The focus-group interviews revealed that the Internet-based tool was well accepted. The Internet-based approach and regular collection of PROs are well accepted with a high participation rate, persistency and adherence in a population of MPN patients. The plasticity of the platform allows for adaptation to patients with other medical conditions.

Results of the PERSIST-1 phase III study of pacritinib (PAC) versus best available therapy (BAT) in primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), or post-essential thrombocythemia-myelofibrosis (PET-MF).

LBA7006 Background: PAC is a potent JAK2 inhibitor without significant JAK1 inhibition with minimal myelosuppression in early-phase studies in MF. Methods: The efficacy and safety of daily oral PAC was compared to BAT (2:1 randomization stratified for risk and platelet count). The 10 endpoint was the proportion of ITT patients (pts) achieving ≥ 35% spleen volume reduction (SVR) at week (wk) 24 by centrally reviewed MRI or CT. Secondary endpoints included the proportion achieving ≥ 50% reduction in total symptom score (TSS) at wk 24 using the MPN Symptom Assessment Form. Results: Patients:327 were enrolled (PAC:220, BAT:107), 62% with 10 MF. Median time from diagnosis was 1.12 years (PAC 0.99, BAT 1.60): 32% and 15% had a platelet counts &lt; 100,000/µL or &lt;50,000/ µL; 75% were JAK2V617F positive. Efficacy: The median duration of treatment was 16.2 months PAC and 5.9 months BAT. Sixty-two percent of BAT patients received active disease directed therapy. The SVR rates at week 24 were 19.1% for PAC vs. 4.7% for BAT (p=0.0003) in ITT and 25% vs. 5.9% (p=0.0001) in the evaluable population. 79% of BAT patients crossed over to PAC; 21% had achieved a &gt;35% reduction in spleen volume at data cutoff. TSS composite V1 + V2 response rates were 24.5%for PAC vs. 6.5% for BAT (p&lt;0.0001) by ITT, and were 40.9% vs. 9.9% in evaluable pts (p&lt;0.0001). Efficacy with baseline cytopenias: In pts with &lt;100,000 and &lt;50,000 platelets/μ/L, the SVR rates were 16.7% for PAC vs. 0% for BAT (p=0.009), and 22.9% vs. 0% (p=0.045) by ITT and 23.5% vs. 0% (p=0.007) and 33.3% vs. 0% (p=0.037) in evaluable pts. In RBC transfusion dependent pts, 25.7% of PAC pts became RBC independent vs. 0% of BAT pts (p=0.043). Safety: The most common adverse events (AE) for PAC were diarrhea, nausea, and vomiting; (grade 3 were &lt;5%, &lt;1%, &lt;1% respectively). Hematologic AEs were similar between PAC and BAT. Conclusions: This study demonstrated PAC was well tolerated and induced significant and sustained SVR and symptom control even in patients with severe thrombocytopenia. PAC therapy resulted in RBC transfusion independence in a significant proportion of pts. Clinical trial information: NCT01773187.

Ruxolitinib Efficacy By Hematocrit Control in Patients with Polycythemia Vera: An Analysis of the RESPONSE Trial

Ruxolitinib Efficacy By Hematocrit Control in Patients with Polycythemia Vera: An Analysis of the RESPONSE Trial

The Efficacy and Safety of Continued Hydroxyurea Therapy Versus Switching to Ruxolitinib in Patients with Polycythemia Vera: A Randomized, Double-Blind, Double-Dummy, Symptom Study (RELIEF)

The Efficacy and Safety of Continued Hydroxyurea Therapy Versus Switching to Ruxolitinib in Patients with Polycythemia Vera: A Randomized, Double-Blind, Double-Dummy, Symptom Study (RELIEF)

Changes in Quality of Life and Disease-Related Symptoms in Patients with Polycythemia Vera Receiving Ruxolitinib or Best Available Therapy: RESPONSE Trial Results

Background: Polycythemia vera (PV) is a myeloproliferative neoplasm driven by JAK/STAT activation and is associated with erythrocytosis and a broad symptom burden that may negatively impact patient quality of life (QoL). Hydroxyurea (HU) is often used as first-line therapy for high-risk patients but may not effectively control or reduce symptom burden. RESPONSE is a phase III trial comparing ruxolitinib (RUX) with best available therapy (BAT) in patients with PV who were intolerant of or resistant to HU according to modified European LeukemiaNet (ELN) criteria. The primary study endpoint (a composite of hematocrit control and ≥35% spleen volume reduction at Week 32) was achieved by 21% of patients in the RUX arm vs 1% in the BAT arm (P<0.0001); 77% of patients in the RUX arm achieved at least one component of the primary endpoint. The current analysis was conducted to evaluate the effect of RUX on PV-related symptoms and QoL measures in the RESPONSE trial.Methods: Patients with PV aged ≥18 years, resistant to or intolerant of HU (modified ELN criteria) with splenomegaly, and who required phlebotomy for hematocrit control were randomized 1:1 to receive open-label RUX 10 mg twice daily (BID) or BAT (administered based on investigator judgment). Dose adjustments were permitted (RUX, 5-mg BID increments [25 mg BID max]; BAT was adjusted per investigator judgment). Objectives of this analysis included assessment of improvement in symptom burden as assessed by patient-reported outcomes using the 14-item modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF), the Pruritus Symptom Impact Scale (PSIS), the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), and the Patient Global Impression of Change. The 14-item MPN-SAF (graded from 0 [absent] to 10 [worst imaginable]) comprised symptoms related to cytokines (tiredness, itching, muscle ache, night sweats, and sweats while awake), hyperviscosity (vision problems, dizziness, concentration problems, headache, numbness/tingling, ringing in ears, and skin redness), and splenomegaly (abdominal discomfort and early satiety). Changes in total symptom score (TSS; maximum score = 140) and individual symptom scores from baseline to Week 32 were summarized by treatment group. For the EORTC QLQ-C30 Global Health Status/QOL score, the percentage of patients with a minimally important difference (MID) from baseline (10-point change) at Week 32 was summarized.Results: Overall, 222 patients were randomized (RUX, 110; BAT, 112). Median age (range) was similar between arms (RUX, 62.0 [34.0–90.0]; BAT, 60.0 [33.0–84.0]); the RUX and BAT arms were 60% and 71% male, respectively. At Week 32, a higher proportion of patients in the RUX vs the BAT arms had a ≥50% improvement in MPN-SAF TSS (49% vs 5%, respectively) and MPN-SAF symptom cluster scores (cytokine, 64% vs 11%; hyperviscosity, 37% vs 13%; splenomegaly, 62% vs 17%). Median percentage changes in individual symptom scores are presented in the Table. Mean changes from baseline at Week 32 on the 5 items of the PSIS indicated that the severity of pruritus and its interference on daily life improved with RUX (range, −1.5 to −2.2) and was unchanged/worsened with BAT (range, −0.1 to 0.3). Treatment with RUX vs BAT was associated with improved mean changes from baseline at Week 32 on EORTC QLQ-C30 symptom subscales, functional subscales, and Global Health Status/QOL (Table); 46% of RUX patients versus 10% of BAT patients achieved an MID in Global Health Status/QOL (Figure). At Week 32, RUX patients were more likely to rate their global impression of symptom changes as “very much improved” or “much improved” (67%) vs BAT patients (13%).Conclusion: In patients with PV who were resistant to or intolerant of HU, treatment with RUX was associated with greater and clinically meaningful improvements in PV-related symptom burden and QoL measures compared with BAT. [Display omitted] [Display omitted] DisclosuresMesa:Incyte Corporation: Research Funding; CTI: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Eli Lilly: Research Funding; Promedior: Research Funding; NS Pharma: Research Funding; Sanofi: Research Funding; Celgene: Research Funding. Off Label Use: Ruxolitinib is a JAK1/JAK2 inhibitor approved for the treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Verstovsek:Incyte Corporation: Research Funding. Kiladjian:Novartis Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Masszi:Novartis Pharmaceuticals: Membership on an entity’s Board of Directors or advisory committees. Durrant:Novartis Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Harrison:Novartis Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. He:Incyte Corporation: Employment, Equity Ownership. Jones:Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Li:Novartis Pharmaceuticals: Employment, Equity Ownership. Côté:Novartis Pharmaceuticals: Employment, Equity Ownership. Habr:Novartis Pharmaceuticals: Employment, Equity Ownership. Vannucchi:Novartis Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding.

Impact of Myeloproliferative Neoplasms (MPNs) on Patients’ Overall Health and Productivity: Results from the MPN LANDMARK SURVEY in the United States

Background: Myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET), are chronic MPNs associated with a broad array of symptoms that may negatively impact patients’ quality of life (QoL). To enhance patient care, it is important to have a current and clear understanding of how MPNs affect the overall health and daily lives of patients. The MPN LANDMARK SURVEY was developed to examine patients’ perceptions of these MPNs related to disease burden, QoL, productivity, and activities of daily living (ADLs).Methods: Eligible patients diagnosed with an MPN were recruited to participate in an online survey conducted from May–July 2014in the US. Patients were asked about the overall burden of disease and impact of symptoms on their QoL, productivity, and ADLs. Descriptive analyses were conducted to assess these outcomes and examined by calculated (not reported) prognostic risk score (MF - DIPSS: Passamonti, Blood 2010; PV: Tefferi, Leuk 2013; ET - IPSET: Passamonti, Blood 2012) and symptom severity quartiles, which were determined using the MPN Symptom Assessment Form (MPN-SAF) total symptom scores.Results: 813 patients (MF=207; PV=380; ET=226) responded to the survey. A majority of patients were female (MF, 54%; PV, 62%; ET, 72%), approximately half were aged 60–74 years (MF, 55%; PV, 51%; ET, 46%), and most were covered by health insurance (>98%). Nearly half (48%) were diagnosed within the last 5 years and average time to diagnosis from first symptoms was >2 years. A high proportion of patients had intermediate to high prognostic risk scores (MF, 94%; PV, 87%; ET, 44%). The majority of patients reported feeling anxious or worried about their MPN (MF, 91%; PV, 78%; ET, 74%). Among all groups, fatigue was the most severe symptom reported (mean MPN-SAF score=6.0–6.4 on a scale of 0–10). A subset of patients in each group described their symptoms as very severe (severity score ≥7 on a scale of 0–10; MF: fatigue [59%], problems with sexual desire [49%], inactivity [46%]; PV: inactivity [48%], fatigue [49%], problems with sexual desire [49%]; and ET: problems with sexual desire [49%], fatigue [50%], headaches [40%]). The majority of patients reported that MPN-related symptoms reduced their QoL (MF, 81%; PV, 66%; ET, 57%); this was reported in all risk groups but more frequently by patients with a high risk score vs a low risk score in MF and ET (MF, 89% vs 69%; PV, 63% vs 65%; ET, 71% vs 59%). A more substantial QoL impact was reported by patients in high vs low symptom quartiles (MF, 95% vs 51%; PV, 94% vs 33%; ET, 93% vs 15%). Similarly, MPNs also had a marked negative impact on reduced work hours, sick days, voluntary job termination, receipt of medical disability, early retirement, and ADLs (Table 1). For example, among patients employed, approximately one fourth reported missing ≥1 day of work (MF, 29%; PV, 19%; ET, 23%) in the last 30 days before the survey. Even patients with low prognostic risk scores often reported missing ≥1 day of work (MF, 33%; PV, 23%; ET, 22%) or cancelling ≥1 day of planned activities (MF, 46%; PV, 35%; ET, 34%). Patients in the high vs low symptom quartiles were more likely to call in sick to work (MF, 48% vs 0%; PV, 52% vs 4%; ET, 38% vs 0%) or cancel ≥1 day of planned activities (MF, 77% vs 5%; PV, 56% vs 7%; ET, 67% vs 3%).Conclusion: The findings from this large, first-of-its-kind survey demonstrate a marked burden of disease across all 3 MPNs that is not limited to symptoms but extends to QoL, productivity, and ADLs. Although high prognostic risk scores have long been associated with a significant burden of disease, in this study, patients with a low risk score also reported significant burden. The symptom burden reported is consistent with previous studies, thus validating the present dataset. MPN treatment considerations should include reducing the symptom burden and improving QoL and productivity to enhance the overall health and lives of MPN patients. [Display omitted] DisclosuresMesa:Incyte Corporation: Research Funding; CTI: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Eli Lilly: Research Funding; Promedior: Research Funding; NS Pharma: Research Funding; Sanofi: Research Funding; Celgene: Research Funding. Miller:Incyte Corporation: Honoraria, Research Funding. Thyne:Incyte Corporation: Speakers Bureau. Mangan:Incyte Corporation: Membership on an entity’s Board of Directors or advisory committees; Alexion Pharmaceuticals: Membership on an entity’s Board of Directors or advisory committees. Goldberger:Incyte Corporation: Membership on an entity’s Board of Directors or advisory committees. Fazal:Incyte Corporation: Consultancy, Research Funding, Speakers Bureau; Gilead: Research Funding, Speakers Bureau. Ma:Incyte Corporation: Consultancy. Wilson:Incyte Corporation: Honoraria. Dubinski:Incyte Corporation: Employment, Equity Ownership. Boyle:ICF International: Employment, Equity Ownership. Mascarenhas:Incyte Corporation: Consultancy, Research Funding; Novartis Pharmaceuticals Corporation: Research Funding.

Real-World Assessment of Clinical Outcomes in Lower-Risk Myelofibrosis Patients Receiving Treatment with Ruxolitinib

Introduction: Published trial data shows that ruxolitinib improves both splenomegaly-related and nonsplenomegaly-related constitutional symptoms in patients with intermediate-2 and high risk myelofibrosis (MF). However, few trial-based assessments of ruxolitinib in lower-risk MF patients have been conducted and no studies to date have made such assessments in a real-world population. In this study, we assessed changes in spleen size and constitutional symptoms during ruxolitinib treatment for lower-risk MF patients in real-world clinical settings.Methods: This was a retrospective, observational review of anonymized medical record data collected in January 2014 by 49 hematologists and oncologists in the United States. Patient inclusion criteria were: (1) diagnosed with lower-risk MF (International Prognostic Scoring System score of 0 or 1); (2) first treated with ruxolitinib ≥3 months before the medical record abstraction date; (3) ≥18 years of age at ruxolitinib initiation; (4) complete medical history from MF diagnosis until the medical record abstraction date; and (5) never enrolled in an MF-related interventional trial. Minimum quotas of n=50 and n=25 were set for intermediate-1 and low-risk patients, respectively, with a predetermined maximum of 110 patients in the combined total. Spleen size and constitutional symptoms were retrospectively observed at MF diagnosis, at ruxolitinib initiation, and at best response while on ruxolitinib. Spleen size was captured via predefined categories of no splenomegaly (spleen not palpable), very mild or mild splenomegaly (<10 cm palpated), moderate splenomegaly (10-20 cm palpated), or severe splenomegaly (>20 cm palpated). Symptoms of interest included those captured in the MPN Symptom Assessment Form (MPN-SAF), which were categorized as mild, moderate, or severe based on medical notes recorded at each time point. For this abstract, we present findings on the 7 most commonly observed MPN-SAF symptoms in our sample. This study was exploratory and used only descriptive analyses.Results: A total of 108 patients were included in the study (25 low-risk and 83 intermediate-1 patients). Ruxolitinib start dates spanned January 2012 – November 2013. All low-risk patients were ≤65 years of age, and nearly 80% of intermediate-1 patients were ≤65 years of age. The majority of patients in both risk groups (60% and 69%, respectively) were male. A higher proportion of intermediate-1 patients were positive for JAK2 V617F mutation (72%) than low-risk patients (56%). Most patients (92% of low-risk, 77% of intermediate-1) were still receiving ruxolitinib treatment at the medical record abstraction date. Median observed ruxolitinib exposure time was approximately 8 months in both risk groups. In low-risk patients, the combined proportion of patients with moderate or severe splenomegaly (≥10 cm palpated spleen) decreased from 64% at MF diagnosis to 16% at best response during ruxolitinib treatment (Figure 1a). Similar findings were observed for intermediate-1 patients: the proportion with moderate or severe splenomegaly decreased from 53% at MF diagnosis to 10% at best response (Figure 1b). General fatigue was the most commonly observed constitutional symptom in both low-risk and intermediate-1 patients (Figures 2a and 2b). Shifts in symptom severity from more severe to less severe were observed in both low-risk and intermediate-1 patients. Among low-risk patients with fatigue, the proportion with moderate or severe fatigue decreased from 90% at MF diagnosis to 37% at best ruxolitinib response; in intermediate-1 patients, the decrease was from 76% at MF diagnosis to 42% at best response. For most other symptoms, similar improvements in severity distribution were observed.Conclusions: Both low-risk and intermediate-1 MF patients experienced a substantial decrease in spleen size from MF diagnosis through ruxolitinib treatment in real-world clinical settings. Furthermore, for most symptoms examined, there was a distinct improvement in the distribution of symptom severity at the time of best response during ruxolitinib treatment. These findings suggest that lower-risk MF patients may benefit clinically from ruxolitinib treatment. Further studies are needed to assess adverse effects and evaluate the benefit-risk tradeoff of ruxolitinib. [Display omitted] [Display omitted] DisclosuresDavis:Novartis Pharmaceuticals Corporation: Research Funding. Kaye:Novartis Pharmaceuticals Corporation: Research Funding. Cote:Novartis: Employment. Off Label Use: The study discusses use of ruxolitinib in patients with lower-risk (IPSS 0 or 1) myelofibrosis (MF) in real-world practice; currently ruxolitinib is only indicated in higher-risk MF (IPSS >1).. Gao:Novartis: Employment. Ronco:Novartis: Employment. Seifeldin:Novartis: Employment. Mendelson:Novartis: Employment.

Burden of Disease and Clinical Responses in Low and Intermediate-1 Risk Myelofibrosis Patients Treated with Ruxolitinib

Myelofibrosis (MF) is a hematologic neoplasm characterized by variable degrees of cytopenias/ myeloproliferation, extramedullary hematopoiesis, disease-related constitutional symptoms and an increased risk for acute myeloid leukemia (AML) transformation. Ruxolitinib, a JAK1/2 inhibitor is FDA approved for the management of intermediate to high-risk MF. However, intermediate-2 and high-risk MF patients accounted for 99% of patients (pts) in the 2 pivotal trials that led to the approval of ruxolitinib in North America, Australia and Europe (COMFORT 1 and COMFORT 2 studies). However, even low and intermediate-1 (int-1) risk MF pts could have a high burden of disease. Here we report our experience of using ruxolitinib in MF pts stratified as low and int-1 risk by the Dynamic International Prognostic Scoring System (DIPSS). A total of 25 pts with low and Int-1 risk disease were treated with ruxolitinib at the Cleveland Clinic and Northwestern University. The median age of the cohort was 61 yrs (range=33-87; males=9, females=16). The median total symptom score (TSS) by Myeloproliferative Neoplasm Symptom AssessmentForm (MPN SAF) was 20. The median pre-treatment spleen size by palpation was 13 cm below the left costal margin. Baseline median bone marrow (BM) fibrosis grading was 2 (on a scale 0-3; grade 1 N=3, grade 2 N=11, and grade 3 N=11). The indications for starting ruxolitinib were constitutional symptoms (fatigue N=20, night sweats N=4, pruritus N=1) and splenomegaly (N=13). The median starting dose was 5 mg twice daily, 10mg twice daily at 3 months and 6 months, and 5mg twice daily at 12 months. The median dose at last follow up was 10 mg twice daily. The median duration of treatment was 12 months. There was a median 73% reduction in the MPN SAF TSS compared to baseline (P< 0.001). There was improvement in each of the parameters of the TSS. The percentage of reduction in spleen size by palpation at 3, 6, 12 months was 49, 57, and 64%, respectively. In 5 patients who had a repeat BM biopsy, there was an improvement in their BM fibrosis by at least 1 grade (N=3), stable fibrosis (N=1) or increased fibrosis (N=1). Hematologic adverse events were reported at 3, 6, 12 months of treatment. Using Common Terminology Criteria for Adverse Events (CTCAEv4.0), there were seven with grade 3/4 anemia and six with grade 3/4 thrombocytopenia. Non-hematologic adverse events reported at 3, 6, 12 months of treatment included dizziness (N=1), headaches (N=1) and infections (pneumonia N=2, cellulitis N=2, perineal abscess N=1, Herpes Zoster N=2, and gluteal abscess after BM biopsy N=1; only one required hospitalization). Ruxolitinib was discontinued in 5 patients due to lack of clinical response (N=3) and grade 3/4 anemia/thrombocytopenia (N=2). The remaining 20 patients are still on treatment. None of the pts progressed to AML or died. The median follow up of our cohort was 27 months. Further, using a multi-Analyte ELISArray Kit, plasma concentrations of interleukins (IL):IL1A, IL1B, IL2, IL4, IL6, IL8, IL10, IL12, IL17A, INFg, TNFa and GM-CSF were measured in low/int-1 risk pts (N=3) and intermediate-2/high risk patients (N=4) and no statistically significant difference was found between the two risk groups (P>0.05) further supporting the high burden of disease observed even in low and int-1 risk MF patients. In conclusion, pts with low/int-1 risk MF have a high burden of disease and can achieve meaningful clinical responses to ruxolitinib similar to int-2/ high risk MF pts without severe toxicity. Larger studies are needed to further evaluate the safety and efficacy of ruxoltinib in this patient population. DisclosuresNo relevant conflicts of interest to declare.

Phase I Study Of LY2784544, a JAK2 Selective Inhibitor, In Patients With Myelofibrosis (MF), Polycythemia Vera (PV), and Essential Thrombocythemia (ET)

BackgroundMF, PV, and ET are neoplasms characterized by activation of JAK2 signaling, and the majority of cases are associated with the gain of function JAK2 V617F mutation. Given that wild-type JAK2 plays a pivotal role in multiple stages of hematopoiesis it is desirable to treat JAK2V617F-positive cases by selectively inhibiting JAK2 V617F while minimizing inhibition of wild-type JAK2 in order not to impede normal marrow function. LY2784544 is a selective inhibitor of JAK2 which demonstrates dose dependent selectivity for JAK2 V617F/STAT5 signaling. LY2784544 entered clinical testing in a Phase I trial in MF, PV, and ET patients (I3X-MC-JHTA, NCT01134120). We have previously reported early interim analysis from this study and provide here an update following completion of study enrollment. MethodsThe study's primary objectives were to determine the safety and tolerability of LY2784544 and define a recommended oral daily dose for further study in patients with JAK2 V617F-positive MF, ET, or PV. Secondary objectives included determination of pharmacokinetics and evaluation of response using the IWG-MRT response criteria (2006), European Leukemia Net response criteria for PV and ET (EULN 2009), and symptom burden using the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) (Scherber et. al. Blood 2011). Study design included a standard 3+3 dose-escalation to define the maximum tolerated dose (MTD) and was amended to allow cohort expansions at multiple doses demonstrating potential clinical merit. ResultsPatients Prior to closing to enrollment, 47 patients were consented; 9 did not meet eligibility screening. The 38 treated patients included 31 MF (22 pMF, 6 post-PV MF and 3 post-ET MF), 6 PVs, and 1 ET patient(s), and 86% had received prior systemic therapy for their MPN.Dosing and tolerability of LY2784544: Systemic exposures were approximately dose proportional across the tested range from 30 to 300 mg. Daily doses of 200 mg or greater were associated with CTCAE Grade 3 increases in serum creatinine. In general, increases in serum creatinine occurred within the first 2 weeks of either starting treatment or after an increase in study drug dose. With the available data, the elevations in serum creatinine appear to be fully reversible after dose reduction or drug holiday in the majority of patients. The maximum tolerated daily dose of LY2784544 when given on a continuous daily basis was determined to be 120 mg per day.Serious AEs, across all grades and doses, included increased creatinine/acute renal insufficiency (4 grade 3, 5 grade 2, 1 grade 1), hyperuricemia (2 grade 4, 1 grade 1), hyperkalemia (1 grade 1), and anemia (1 grade 3). This study allowed intrapatient dose escalation, and 34 patients received 120 mg during their study participation. There were 4 patients dosed at 120 mg with SAEs but all were unrelated to study drug treatment (anemia, influenza, enterococcal bacteremia, hematuria and pneumonia). At 120 mg, the most frequently reported drug-related AEs across all grades were diarrhea (44%), nausea (29%), increased creatinine (21%), and anemia, vomiting, fatigue (9% each). Of these related AEs at 120 mg, there was 1 Grade 3 anemia, 3 Grade 3 increased creatinine, and 2 Grade 3 fatigue. There were no Grade 4 AEs. EfficacyAmong a cohort of 10 MF patients who only received 120 mg, 3 achieved a clinical improvement. Analyzing across dose levels, a palpable spleen length reduction of ≥50% was seen in 15 of 27 evaluable patients (56%) at any time. The median duration of these responses was 18.3 weeks (range from 0.7 to 148.1 weeks). At 12 weeks, 56% of patients (15/27) reported a ≥50% improvement in Total Symptom Score on the MPN-SAF. Of the 6 PV patients, 3 achieved a clinicohematologic PR. Findings from a central pathology review of serial bone marrow samples will be presented at the meeting. ConclusionsA recommended phase II dose for daily dosing of LY2784544 was identified as 120 mg. This dose has been well tolerated and associated with clinical improvements, supporting ongoing Phase II testing of LY2784544 in MPNs. Disclosures:Verstovsek:Eli Lilly and Co: Research Funding. 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. Salama:Eli Lilly and Co: Research Funding. Giles:Eli Lilly and Co: Employment. Pitou:Eli Lilly and Co: Employment. Hayden Zimmermann:Eli Lilly and Co: Employment. Price:Eli Lilly and Co: Employment. Walgreen:Eli Lilly and Co: Employment. Prchal:Eli Lilly and Co: Research Funding.

Baseline Characteristics and Symptom Burden in RESPONSE: A Randomized, Open-Label, Phase 3 Study of Ruxolitinib In Polycythemia Vera Patients Resistant to or Intolerant of Hydroxyurea

Abstract Background Polycythemia vera (PV) is the most common of the myeloproliferative neoplasms and is characterized by elevated hematocrit requiring phlebotomy, splenomegaly, a variety of symptoms and increased thrombotic risk. Ruxolitinib, a JAK1/JAK2 inhibitor, was well tolerated and achieved rapid and durable clinical responses in a phase 2 study of patients (pts) with PV who were resistant to or intolerant of hydroxyurea (HU). Pts experienced phlebotomy independence, resolution of splenomegaly, and improvements in white blood cell (WBC) counts, platelet (PLT) counts, and disease-related symptoms. Here, we describe the baseline (BL) characteristics and symptom burden of pts in a phase 3 study of ruxolitinib in pts with PV who are resistant to or intolerant of HU. Methods RESPONSE is a randomized (1:1), open-label, phase 3 study (NCT01243944) comparing the efficacy and safety of ruxolitinib with best available therapy (BAT) in pts with PV who are resistant to or intolerant of HU (modified European LeukemiaNet criteria), have splenomegaly, and require phlebotomy for inadequate hematocrit (Hct) control. Fourteen disease-related symptoms were assessed on a scale of 0 (absent) to 10 (worst imaginable) using the modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF). Blinded data are presented here. Results BL demographic data are available for the 222 enrolled pts (Table). Apart from HU, other common prior medications for PV included interferons (15%), PLT aggregation inhibitors (10%), alkylating agents (3.6%), alkyl sulfonates (3.2%), pyrimidine analogues (1.8%), and nitrosoureas (1.4%). The majority of pts (54.5%) had 1 phlebotomy within 12 weeks prior to screening; 23.9% had 2 and 17.1% had 3 or more phlebotomies. RESPONSE BL demographics are generally similar in terms of age (60 years vs 57-67); sex (66% male vs 58%-68%); Hct (44% vs 45%-48%); and platelets (419 x 109/L vs 320-429 x 109/L) to other PV studies including trials of givinostat (Finazzi BJH 2013) and AOP2014 (Gisslinger ASH 2012) and the ECLAP-PV (Marchioli JCO 2005) and CYTO-PV studies (Marchioli NEJM 2012). At the time of writing, BL symptom data from the MPN-SAF were available for 164 pts (Table). Pts in this study reported a similar symptom burden as PV pts from a large study of pts with MPNs (Emanuel JCO 2012; N = 1425; PV, n = 538), including similar mean scores for early satiety, abdominal discomfort, concentration problems, night sweats, itching, and tiredness/fatigue. In addition, prior therapy may have adversely affected BL symptom burden, as many of these symptoms (concentration problems, night sweats, fatigue) have been shown to be worsened by the use of conventional therapy to strictly control Hct (&lt; 45%) and cardiovascular risk (Emanuel EHA 2013). BL MPN-SAF symptom data for all 222 pts will be presented. In addition, correlations between BL EORTC QLQ-C30 and MPN-SAF scores will be presented. Summary/Conclusions Demographic and BL symptom data from the RESPONSE study demonstrated that pts with HU refractory or intolerant PV have a significant disease burden that includes a variety of symptoms. These findings are consistent with those of Emanuel (JCO 2012), which showed that pts with PV have a significant symptom burden and a reduced quality of life. Pts with PV in the RESPONSE study are representative of those who have been studied in other clinical trials for the treatment of PV. Disclosures: Vannucchi: Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Off Label Use: Ruxolitinib, a JAK1/JAK2 inhibitor, has been approved by the US Food and Drug Administration for the treatment of intermediate- or high-risk MF and by the European Commission and Health Canada for the treatment of disease-related splenomegaly or symptoms in adult patients with MF. Here, we describe the baseline (BL) characteristics and symptom burden of patients in a phase 3 study of ruxolitinib in patients with PV who are resistant to or intolerant of HU. Kiladjian:Novartis: Honoraria; Shire: Honoraria. Durrant:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Sanofi: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Pane:Novartis: Consultancy, Honoraria; Shire: 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; 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. He:Incyte: Employment. Leopold:Incyte: Employment, Stock options Other. Li:Novartis: Employment, Equity Ownership. Pirron:Novartis: Employment, Equity Ownership. Lawniczek:Novartis: Employment. Verstovsek:Incyte: Research Funding.

Myeloproliferative (MPN) Symptom Burden Response Thresholds: Assessment Of MPN-SAF TSS Quartiles As Potential Markers Of Symptom Response

BackgroundWe have previously reported on the significant, but heterogeneous baseline MPN symptom burden among an international sample of MPN patients (including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF)) utilizing the MPN Symptom Assessment Form (MPN-SAF) and the derivative Total Symptom Score (MPN-SAF TSS). Recent clinical trials have sought to determine optimal MPN symptom response criteria, such as absolute 10 point improvement in MPN SAF TSS for ET/PV (ELN Criteria, Barosi et. al. Blood 2013) and 50% reduction in MPN-SAF TSS for MF (IWG-MRT, Tefferi et. al. Blood 2013). We sought to determine the role of improvement in MPN-SAF TSS quartiles as potential thresholds to assess symptomatic response to therapy. MethodsUtilizing prospectively gathered MPN-SAF TSS (Emanuel et. al. JCO 2012) in patients we assessed potential thresholds of response by evaluating quartile thresholds for severity of symptom burden. The MPN-SAF TSS was scored as the average of 10 symptoms (individual symptoms scores of 0-10, with a total score of 0 (best) to 100 (worst)). MPN-SAF TSS quartiles were identified by the percentage of scores between 0-24% (quartile 1 (Q1)), 25-49% (quartile 2 (Q2)), 50-74% (quartile 3 (Q3)), 75-100% (quartile 4 (Q4)). ResultsMPN-SAF TSS Quartiles: MPN-SAF TSS quartiles were identified among 1858 MPN patients (ET N=775, PV N=654, and MF N=423). Overall MPN-SAF TSS scores of 0 - 7 were designated as Q1, 8 - 17 as Q2, 18 - 31 as Q3, and ≥ 32 was as Q4. MPN-SAF TSS scores were significantly different between clusters (p<0.001).Associations Between Quartiles and Demographic/ Disease Factors: As quartiles increased, the proportion of PV and ET patients diminished and MF increased (Table 1, p<0.001). Cytopenias and transfusion dependence increased in prevalence in the higher quartiles (p<0.001). A history of prior thrombosis was also significantly more prevalent in the quartiles with highest symptom burden (p<0.001). The prevalence of women was significantly higher among the more symptomatic quartiles females 48.9% Q1, 49.4% Q2, 58.4% Q3, and 60.1% Q4; p<0.001).Associations Between Individual Symptoms and MPN-SAF TSS Quartiles: All individual symptoms measured in the MPN-SAF TSS were significantly worse in quartiles as they increased (p<0.0001).Evaluation of Prognostic Scoring and MPN-SAF TSS Quartiles: Comparison of each patients individual risk score (IPSET, PV, DIPSS for MF) and worsening symptom quartile showed the highest correlation with MF patients (DIPSS) (Table 1). However, ET and PV risk scores were not surrogates for symptom burden by quartile. ConclusionsDistribution of MPN patient symptomatic burden by MPN-SAF TSS quartiles provides an easy-to-calculate method to cluster and analyze MPN patients of similar burden. Although MF patients are most prevalent in the most severe quartile of MPN symptomatology it is notable that Q4 has many patients with PV and ET. Future prospective efforts are ongoing to assess the potential of using changes in quartile (i.e. improving from Q3 to Q1) as potential symptomatic response thresholds. 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:Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; S Bio: Honoraria, Membership on an entity's Board of Directors or advisory committees; Shire: Speakers Bureau; Celgene: Honoraria; YM Bioscience: 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, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Vannucchi:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Birgegard:Vifor Pharma: Honoraria.

Revised response criteria for myelofibrosis: International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report

AbstractThe current document is a revision of the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria for treatment response in myelofibrosis (MF) and represents a collaborative effort by the IWG-MRT and the European LeukemiaNet to objectively assess the value of new drugs in inducing morphologic remission or improvement in MF-associated symptomatic burden (MF-SB). Some of the changes in the current revision include stricter definitions of red cell transfusion dependency and independency and consideration of the Myeloproliferative Neoplasm Symptom Assessment Form as a tool to quantify meaningful changes in disease-related symptoms. Six response categories are listed: complete remission (CR) and partial remission signify treatment effects that are consistent with disease modification, whereas drug-induced improvements in MF-SB were annotated as clinical improvement, anemia response, spleen response, or symptoms response. Additional criteria are provided for progressive disease, stable disease, and relapse. The document also includes recommendations for assessing cytogenetic and molecular remissions, without mandating their inclusion for CR assignment.

Patients with polycythemia vera have worst impairment of quality of life among patients with newly diagnosed myeloproliferative neoplasms

The quality of life (QoL) at the time of diagnosis of myeloproliferative neoplasm (MPN) has, to date, not been studied. One hundred and seventy-nine patients with MPN: 80 with essential thrombocythemia (ET), 73 with polycythemia vera (PV), 22 with primary myelofibrosis (PMF) and four with MPN undifferentiated, were included in this study. European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQC30) and the MPN-Symptom Assessment Form (MPN-SAF) were used to evaluate QoL. Fatigue was the most reported symptom in these patients. Patients with PV reported significantly higher mean scores for inactivity, dizziness, cough, itching, depression and lower total QoL compared to patients with ET. Patients with PV had significantly more headache and itching compared to patients with PMF. When the newly diagnosed patients with MPN were compared with a cohort of patients with MPN with mean disease duration of 7.8 years, the differences were most striking for patients with PMF, with significantly more fatigue, abdominal discomfort, concentration problems, insomnia, fever, weight loss and lower overall QoL developed over time.