ALBERT

Beschreibung: MAJIC is a phase II trial of Ruxolitinib (RUX) vs Best Available Therapy (BAT) in essential thrombocythemia (ET) patients with resistance/intolerance to Hydroxycarbamide (HC) per European LeukemiaNet (ELN) criteria. Primary outcome was rate of complete hematological response (CHR) within 1 year (ELN criteria); secondary outcomes included partial HR, safety, thrombosis, hemorrhage, progression free survival (including transformation), molecular response (MR), symptom & quality of life (QOL) assessment. We present new data concerning molecular, symptom & clinical responses. Patients were stratified by JAK2V617F status, patient-reported symptoms & QOL determined using EQ5D, MDASI & MPN Symptom Assessment Form (MPN10), & compared using linear mixed models of post-baseline scores through month 12 adjusting for baseline; response was defined as ≥50% reduction in MPN10 total symptom score (TSS). JAK2/CALR/MPL allele burdens were assessed at baseline & 4 monthly. 110 patients were eligible for the modified ITT analysis, 58 (52%) & 52 (48%) in RUX & BAT arms respectively, comprising 44 males, 66 females, mean age 64.2ys, & resistant (24.5%), intolerant (51.8%) or both (22.7%) to HC. CHR was achieved in 27 (46.6%) of RUX patients vs 23 (44.2%) BAT patients (χ2 test p= 0.81). PHR occurred in 26 (44.8%) & 27 (51.9%) of RUX & BAT treated respectively. Grade 3 or 4 anemia occurred in 19% & 0% for RUX arm vs 0% (both grades) for BAT arm, grade 3 or 4 thrombocytopenia in 5.2% & 1.7% of RUX vs 0% (both grades) of BAT patients respectively. Grade 3 or 4 infections occurred in 10.3% of RUX patients vs 3.6% BAT arm. 9 RUX treated patients had 10 thrombotic events & 1 RUX patient a hemorrhage; vs 5 thrombotic & 5 hemorrhagic events in BAT patients (adjusted following central review). Transformations to post-ET MF occurred in 8 RUX vs 3 BAT treated patients, 1 RUX patient developed AML. 2 non-treatment related deaths occurred in each arm. Mean MPN-10 TSS & individual symptoms of early satiety & itching during the first 12 months were all significantly lower for RUX vs BAT (all p

Beschreibung: Background: Patients with acute myeloid leukemia (AML) face poor outcomes and treatments with significant and debilitating toxicities. New regimens with improved efficacy and an improved side effect profile are needed. Documenting patient experience can assist in identifying unmet needs and in fostering drug development. We sought to understand the experience of patients with AML by prioritizing their AML-related worries as part of a larger patient-focused drug development initiative led by The Leukemia & Lymphoma Society. Methods: A robust community-centered approach was used to engage diverse expert and community stakeholders in the development of an instrument to prioritize patient worry. A pilot study was completed to refine the instrument which resulted in 13 patient-centered worries encompassing decision-making, treatment delivery, physical side effects, and psychosocial effects. To capture best-worst (BW) scores, patients were presented with repeated choice tasks prompting them to choose the attributes that they were most and least worried about among repeated subsets of attributes chosen using a balanced-incomplete block design. Results were analyzed using a conditional logistic regression with patients' choices of attributes as the dependent variable. A national survey of patients and caregivers was conducted with the instrument. Results were then compared with Likert ratings of the attributes for validation. Sub-group analysis compared patients currently in remission to those not in remission. Additional qualitative worries were also collected. Results: The survey was delivered to 5,353 potential participants. A total of 892 patients with AML participated; 832 completed all choice tasks. Patients were predominantly white (88%), married or partnered (72%), college-educated (66%), and privately-insured (79%). Many were currently employed (46%) while some were disabled (25%) or retired (22%). Most patients received an allogeneic stem cell transplant (64%) and the large majority (95%) were currently in remission. The mean time from diagnosis was 8 years (range = 1 - 40), and the mean age was 55 years (range = 19 - 87). Patients were most worried about "the possibility of dying from AML" (Regression result = 1.25, Standard Error (SE) = 0.030), followed by "long-term side effects of treatments" (Regression result = 1.05, SE = 0.030), "being a burden to others" (Regression result = 0.32, SE 0.029), and "returning to daily activities" (Regression result = 0.31, SE 0.028). Patients were least worried about "communicating openly with doctors" (Regression result = -1.25, SE 0.030), "having access to the best medical care" (Regression result = -0.75, SE 0.029) and "having enough information about AML" (Regression result = -0.62, SE 0.028). BW scores were highly correlated with Likert ratings (Spearman's rho = 0.93). Patients who were not in remission worried more about "knowing about all the treatment options" than "coping with the emotional demands of AML," "short-term side effects of treatments," "the overall financial cost of AML," and "choosing a treatment in a short amount of time." Overall, patients found it easy to understand the questions (78%), easy to answer all the questions (64%) and answered the questions consistently with their experience (89%). Conclusions: Identifying and prioritizing the worries of patients with AML are necessary to understand the experience of those affected by the disease. In this large, national sample representing mostly AML survivors, patients had the strongest worries about long-term clinical outcomes including the possibility of dying from their disease and the long-term side effects of therapy. Psychosocial effects were also worrisome including concerns about burdening others, returning to work, emotionally coping with AML, and the cost of treatment. Items related to treatment delivery and decision-making were less prioritized, perhaps illustrating the sufficient expertise and counseling from care providers. Patients who were not in remission were more concerned about understanding treatment options. Representing the largest study to date of the concerns of patients with AML, these data can serve to inform patient care and the development of new treatment options. Figure. Figure. Disclosures O'Donoghue: The Leukemia & Lymphoma Society: Employment. Bridges:The Leukemia & Lymphoma Society: Research Funding.

Beschreibung: Background: Myeloproliferative neoplasms (MPN) including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) are clonal hemopathies characterized by burdensome symptom profiles and impaired quality of life. Few studies have evaluated patient-reported outcomes during treatment with non-experimental pharmacological regimens. Aims: The Myeloproliferative Neoplasm Quality of Life (MPN-QOL) Study Group aims to objectively quantify MPN symptom severity, frequency and quality of life at baseline and throughout treatment with non-experimental therapies utilizing the Myeloproliferative Neoplasm Symptom Assessment Form - Total Symptom Score (MPN-SAF TSS; JCO 2012). In this abstract, we provide updated results for the prospective international cohort trial currently in active enrollment: the MPN Experimental Assessment of Symptoms by Utilizing Repetitive Evaluation (MEASURE) trial. Methods: This study aims to recruit 180 international ET, PV, and MF (including primary MF and post-ET or post-PV MF) patients receiving non-experimental medical therapy and/or phlebotomy. Patients complete the MPN-SAF for seven consecutive days at enrollment and repeat the survey for an additional seven consecutive days between 90 days and six months. Patients also complete the European Organisation for Research and Treatment of Cancer (EORTC) and M.D. Anderson Symptom Inventory (MDASI) instruments at enrollment and on the first day of the second assessment. At visits, physicians acquired demographic, laboratory, physical examination, and radiographic data. Descriptive statistics were used to summarize data. Results: Clinical Data The MEASURE trial opened for enrollment in 2012 and remains in recruitment phase with 15 participating international sites. To date, 39 patients have been enrolled and 25 have completed both study visits. Participants include ET (28%), PV (24%), and MF (48%; 50% primary MF, 8% post-ET, 42% post-PV) patients. The majority of patients are male (64%) and of expected age (mean 69.3, range 39-89) for the disorders. Seventeen percent had prior thrombosis, 9% required red blood cell transfusion, and none reported prior splenectomy or hemorrhage. Mean hematologic measures included hemoglobin 13.2 g/dL, WBC count 11.4 x109/L, ANC 8.5 x109/L, and platelets 514 x109/L. Therapies received prior to enrollment included aspirin (n=16), hydroxyurea (n=11), phlebotomy (n=8), warfarin/clopidogrel/anticoagulation (n=8), erythropoietin (n=2), and interferon (n=1). The most common current MPN therapies were hydroxyurea (n=9), aspirin (n=9), interferon (n=4), and phlebotomy (n=2). Symptom Assessment In comparing MPN-SAF TSS mean symptom scores, all symptoms except bony pain improved between the first and second visits, including fatigue, early satiety, abdominal discomfort, inactivity, concentration, night sweats, itching, fever, weight loss, and overall quality of life (Figure1). Total MPN-SAF TSS scores improved from a mean of 32.3 to 25.9. On the EORTC, mean scores for physical, role, emotional, and social functioning improved from the first to the second visit (Figure 2). Cognitive functioning showed a slight decline. Global health status measure improved from 60.2 to 72.9. On the MDASI, symptom severity scores decreased from 3.6 to 2.8 from the first to second visit (Figure 3). Symptom distress measure decreased from 4.1 to 3.0. Discussion: Interim results from the MEASURE trial demonstrate that standard, non-experimental treatment regimens offer improvement in quality of life-related symptoms on multiple patient-reported survey instruments including the MPN-SAF TSS, EORTC QLQ-C30, and MDASI. Updated data including symptom correlations and mutational analysis to be presented at the 2016 ASH conference. Disclosures Ross: Novartis Pharmaceuticals: Honoraria, Research Funding; BMS: Honoraria. Radia:Novartis: Honoraria; Pfizer: Honoraria. McMullin:Novartis: Honoraria, Speakers Bureau. Cargo:Novartis: Honoraria; Celgene: Honoraria, Research Funding. Sekhar:Novartis: Research Funding. Mesa:Gilead: Research Funding; CTI Biopharma: Research Funding; Galena: Consultancy; Ariad: Consultancy; Incyte: Research Funding; Novartis: Consultancy; Celgene: Research Funding; Promedior: Research Funding.