Myelofibrosis (MF) is a clonal hematopoietic malignancy characterized by constitutional and localized symptoms, progressive splenomegaly, bone marrow fibrosis, and cytopenias. Although MF is well studied, few studies exist regarding its symptomatic burden in routine clinical practice. This study aimed to characterize symptoms and other clinical features of MF among patients in the United States. We conducted a retrospective medical record review of adult patients with an MF diagnosis between 1 January 2005 and 31 March 2010, stratified by the presence of palpable splenomegaly. Eligible patients had 12 months or more of follow-up after diagnosis (or after detection of splenomegaly, if present) unless death occurred. Demographic and clinical characteristics, MF-related symptoms, and treatments were reported by treating physicians. We report on 180 MF patients: 102 with splenomegaly, 78 without. Median age was 66 years, 63% were male, and 82% had intermediate-2 or high-risk MF (International Prognostic Scoring System). Fatigue was reported by ∼85% of patients; weight loss, night sweats, and fever (any grade) were each reported by 50% or more of patients. Generalized abdominal pain, left subcostal pain, and early satiety occurred more frequently among patients with splenomegaly. Multiple symptoms were reported by 95% of patients. Common comorbidities were hypertension, diabetes, and chronic pulmonary disease. Symptoms are common in MF patients, regardless of the presence of palpable splenomegaly. Careful assessment of symptom burden is an important aspect of the clinical evaluation of patients with MF.

BackgroundHydroxyurea (HU) is among the most commonly used cytoreductive treatments for polycythemia vera (PV), but previous research and clinical experience suggest that not all patients respond optimally, consistently, or durably to HU treatment. This study investigated patterns of HU use and impact on disease control among patients with PV in real-world clinical practice in the United States.MethodsOncologists and hematologists recruited between April and July 2014 reported data from patient charts. Treatment history and disease symptom comparisons between HU subgroups were performed using Chi square tests or one-way analyses of variance for categorical and continuous variables. Other analyses were performed using descriptive statistics.ResultsOverall, 329 physicians participated and provided data on 1309 patients with PV (62.3 % male; mean age = 62.5 years, mean time since diagnosis = 5.2 years). In the 229 (17.5 %) patients who had stopped HU, the most common reasons for HU discontinuation—as assessed by the treating clinician—were inadequate response (29.3 %), intolerance (27.5 %), and disease progression (12.7 %). Among patients currently on HU, a significant proportion had elevated blood cell counts: 34.4 % had hematocrit values ≥45 %, 59.4 % had platelet levels >400 × 109/L, and 58.2 % had WBC counts > 10 × 109/L. Two-thirds (66.3 %) of patients had ≥1 elevated count, 40.3 % had ≥2 elevated counts, and 19.8 % had all 3 counts elevated. The most common PV-related signs and symptoms among all patients were fatigue and splenomegaly.ConclusionsAlthough many patients with PV benefit from HU therapy, some continue to have suboptimal control of their disease, as evidenced by persistence of abnormally elevated blood cell counts and the continued experience of disease-related manifestations (signs and symptoms). These data further denote a significant medical need for some patients with PV currently or previously treated with HU.Electronic supplementary materialThe online version of this article (doi:10.1186/s40164-016-0031-8) contains supplementary material, which is available to authorized users.

Background: PV is a myeloproliferative neoplasm characterized by increased red cell mass and elevated hematocrit. Phlebotomy represents the initial treatment option to lower hematocrit with the goal of reducing the risk of thrombosis. However, many patients require cytoreductive therapy, HU being the most commonly used treatment. Based on European LeukemiaNet (ELN) guidelines, response to PV therapies includes clinicohematologic response (CHR) which is based on several laboratory parameters (hematocrit values, platelet count, white blood cell count) as well as disease-related symptoms. The aim of this study was to investigate the treatment patterns, outcomes, and unmet medical needs among patients with PV treated with HU in a real-world setting. Methods: A retrospective chart review of PV patients was conducted in the United States between April-July 2014. Oncologists and hematologists abstracted data from patient charts into an online survey. Physicians were eligible to participate if they spent ≥50% of their time on direct patient care and had ≥5 PV patients under their care in the past 12 months with at least 25% of whom had prior (if not current) HU experience. Initial individual qualitative interviews with a subset of eligible physicians (N=19) were conducted to inform the design of the survey instrument. A pilot test survey with 28 physicians meeting eligibility was conducted to demonstrate feasibility and included in the final analyses. Inclusion criteria for patient charts were: age≥18 years, alive at time of chart abstraction or deceased within the past 6 months, diagnosed with PV 3-15 years ago, received HU therapy for ≥2 months within the last 5 years, had medical record data 12 months pre- and post-HU initiation, and were not part of a PV-related clinical trial. Treatment history, lab values, disease symptoms, and healthcare resource utilization data were collected and reported descriptively. Results: A total 329 physicians participated (Hem Oncs=78.1%, Med Oncs=15.5%, and hematologists=6.4%) and provided information on 1309 PV patients. Almost two-thirds (62.3%) of patients were male, mean age was 62.5 years (SD=12.2), and mean time since diagnosis was 5.2 years (SD=2.8). Among those currently on HU therapy (n=1,080; 82.5%), mean duration of therapy was 47.0 months (SD=30.8) and mean daily dose was 984 mg (SD=674 mg). A total of 229 (17.5%) of patients had discontinued HU therapy. Prior to discontinuing HU treatment, mean therapy duration was 23.2 months (SD=24.5), and mean daily dose immediately prior to discontinuing was 991 mg (SD=689 mg); 27.3% (n=183) of patients had a dose adjustment in the 3 months prior to discontinuing (range: 1-8 adjustments). The most common reasons for HU discontinuation were elevated hematocrit (23.1%) and the presence of drug-related side effects (21.8%) (Figure 1). Among those currently on HU, a significant proportion had elevated blood counts above ELN response thresholds: 34.4% had hematocrit level ≥45%, 59.4% had platelet levels >400x109/L, and 58.2% had WBC >10x109/L. Two-thirds (66.3%) of patients had at least one elevated value, 40.3% had at least two elevated values, and 19.8% had all three elevated. The most commonly observed PV-related signs and symptoms were fatigue (62.2%) and splenomegaly (57.3%). Furthermore, among patients currently on HU therapy, almost half (46.2%) experienced new PV-related symptoms in the past 12 months, the most common of which fatigue (22.7%) and splenomegaly (19.5%) in the past 12 months. Conclusions: In our study, a significant number of patients with PV discontinued HU therapy due to a lack of effectiveness or tolerability. Of those still on HU therapy, the majority did not achieve ELN response criteria for CHR. Furthermore, nearly half of the patients experienced new PV-related symptoms fatigue and splenomegaly despite HU treatment. Consistent with other reports, these study findings demonstrate that despite HU treatment, many patients continue to have uncontrolled PV. These data further support the significant unmet medical need in PV, including the need for more effective treatment options. Figure 1. Reasons for discontinuation among those who discontinued HU (N=229). Figure 1. Reasons for discontinuation among those who discontinued HU (N=229). Disclosures Parasuraman: Incyte Corporation: Employment, Equity Ownership. 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. DiBonaventura:Incyte Corporation: Research Funding. Reith:Incyte Corporation: Employment, Equity Ownership. Concialdi:Incyte Corporation: Research Funding.