Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-17-2014 | Award Amount: 6.00M | Year: 2015
Myelodysplastic syndromes (MDS) are chronic bone marrow malignancies of the elderly, complicated by severe anaemia. MDS significantly affects quality-adjusted survival and it imposes an increasing financial burden on patients and healthcare (HC) systems. The burden of disease is expected to worsen in the future, given the aging EU population and newly identified MDS cases among those diagnosed with Anaemia of the Elderly. EUMDS - a unique registry with prospective, observational data on 1600 lower-risk MDS patients from 16 EU countries - enables comparison of existing MDS HC interventions (HCI). Objectives 1) Comparison of outcomes and costs of existing HCI, using established and new core outcome sets. This, alongside health technology assessment, will provide robust evidence to underpin sustainable use of HC resources; 2) Enhanced compliance with diagnostic procedures in MDS by introducing new minimally-invasive diagnostic methods. This will increase the number of correctly and timely diagnosed MDS patients; 3) Raised awareness of the relevance of obtaining the right diagnosis in elderly by comparing HRQoL between EUMDS and against a non-MDS cohort. This will improve HRQoL of individual patients through better tailoring of HCI; 4) Better outcome predictability of available HCI by refining classification of cases using molecular characterisation to incorporate response to HCI and to provide evidence for personalised medicine; 5) Improved, evidence-based, guidelines supporting the regulatory process, and providing information to patients and physicians to promote personalised decisions in MDS care; 6) Establishment of a European MDS competence network encompassing all stakeholders in the MDS field. Relevance Better treatment compliance, a more evidence-based use of HCI and an increasing tailored use of existing HC options will contribute to an efficient and cost effective (personalised) use of HC resources for elderly patients with MDS and their co-morbidities.
PubMed | University of Limoges, Institute Paoli Calmettes, and University Paris, Laboratoire dhematologie and 12 more.
Type: Journal Article | Journal: Haematologica | Year: 2016
The efficacy of azacitidine in patients with anemia and with lower-risk myelodysplastic syndromes, if relapsing after or resistant to erythropoietic stimulating agents, and the benefit of combining these agents to azacitidine in this setting are not well known. We prospectively compared the outcomes of patients, all of them having the characteristics of this subset of lower-risk myelodysplastic syndrome, if randomly treated with azacitidine alone or azacitidine combined with epoetin-. High-resolution cytogenetics and gene mutation analysis were performed at entry. The primary study endpoint was the achievement of red blood cell transfusion independence after six cycles. Ninety-eight patients were randomised (49 in each arm). Median age was 72 years. In an intention to treat analysis, transfusion independence was obtained after 6 cycles in 16.3% versus 14.3% of patients in the azacitidine and azacitidine plus epoetin- arms, respectively (P=1.00). Overall erythroid response rate (minor and major responses according to IWG 2000 criteria) was 34.7% vs. 24.5% in the azacitidine and azacitidine plus epoetin- arms, respectively (P=0.38). Mutations of the SF3B1 gene were the only ones associated with a significant erythroid response, 29/59 (49%) versus 6/27 (22%) in SF3B1 mutated and unmutated patients, respectively, P=0.02. Detection of at least one epigenetic mutation and of an abnormal single nucleotide polymorphism array profile were the only factors associated with significantly poorer overall survival by multivariate analysis. The transfusion independence rate observed with azacitidine in this lower-risk population, but resistant to erythropoietic stimulating agents, was lower than expected, with no observed benefit of added epoetin, (clinicaltrials.gov identifier: 01015352).
Germing U.,Heinrich Heine University Düsseldorf |
Lauseker M.,Ludwig Maximilians University of Munich |
Hildebrandt B.,Heinrich Heine University Düsseldorf |
Symeonidis A.,University of Patras |
And 28 more authors.
Leukemia | Year: 2012
Myelodysplastic syndromes (MDS) with del(5q) are considered to have a benign course of the disease. In order to address the issue of the propensity of those patients to progress to acute myeloid leukemia (AML), data on 381 untreated patients with MDS and del(5q) characterized by low or intermediate I International Prognostic Scoring System (IPSS) risk score were collected from nine centers and registries. Median survival of the entire group was 74 months. Transfusion-dependent patients had a median survival of 44 months vs 97 months for transfusion-independent patients (P>0.0001). Transfusion need at diagnosis was the most important patient characteristic for survival. Of the 381 patients, 48 (12.6%) progressed to AML. The cumulative progression rate calculated using the Kaplan-Meier method was 4.9% at 2 years and 17.6% at 5 years. Factors associated with the risk of AML transformation were high-risk World Health Organization adapted Prognostic Scoring System (WPSS) score, marrow blast count >5% and red-cell transfusion dependency at diagnosis. In conclusion, patients with MDS and del(5q) are facing a considerable risk of AML transformation. More detailed cytogenetic and molecular studies may help to identify the patients at risk of progression. © 2012 Macmillan Publishers Limited.
Khellaf M.,University Paris Est Creteil |
Michel M.,University Paris Est Creteil |
Quittet P.,Montpellier University Hospital Center |
Viallard J.-F.,CHU Haut Leveque |
And 21 more authors.
Blood | Year: 2011
Romiplostim, a thrombopoietic agent with demonstrated efficacy against immune thrombocytopenia (ITP) in prospective controlled studies, was recently licensed for adults with chronic ITP. Only France has allowed romiplostim compassionate use since January 2008. ITP patients could receive romiplostim when they failed to respond to successive corticosteroids, intravenous immunoglobulins, rituximab, and splenectomy, or when splenectomy was not indicated. We included the first 80 patients enrolled in this program with at least 2 years of follow-up. Primary platelet response (platelet count ≥ 50 × 10 9/L and double baseline) was observed in 74% of all patients. Long-term responses (2 years) were observed in 47 (65%) patients, 37 (79%) had sustained platelet responses with a median platelet count of 106 × 10 9/L (interquartile range, 75-167 × 10 9/L), and 10 (21%) were still taking romiplostim, despite a median platelet count of 38 × 10 9/L (interquartile range, 35-44 × 10 9/L), but with clinical benefit (lower dose and/or fewer concomitant treatment(s) and/or diminished bleeding signs). A high bleeding score and use of concomitant ITP therapy were baseline factors predicting romiplostim failure. The most frequently reported adverse events were: arthralgias (26%), fatigue (13%), and nausea (7%). Our results confirmed that romiplostim use in clinical practice is effective and safe for severe chronic ITP. This trial was registered at www.clinicaltrials.gov as #NCT01013181. © 2011 by The American Society of Hematology.
Ades L.,Groupe Francophone des Myelodysplasies |
Sekeres M.A.,Cleveland Clinic |
Wolfromm A.,Groupe Francophone des Myelodysplasies |
Teichman M.L.,H. Lee Moffitt Cancer Center and Research Institute |
And 7 more authors.
Leukemia Research | Year: 2013
Treatment of CMML remains a clinical challenge, with no drug demonstrating clear clinical benefit. Even if azacitidine is approved in the treatment of CMML, its role remains disputed. We report a cohort of 76 CMML patients (according to WHO classification) treated with azacitidine in 3 programs (French AZA compassionate program, Cleveland Clinic Foundation and H. Lee Moffitt Cancer Center). 45% had CMML2, and 55% had splenomegaly and/or WBC counts >13. G/L, which are known to be poor prognostic factors in CMML. All patients received AZA for at least one cycle, and the median number of cycles administered was 6. Thirty-three patients (43%) achieved a response according to IWG 2006 criteria, including 13 complete remissions (17%). Median survival was 29 months. Increased bone marrow blast percentage and proliferative features of the disease, including splenomegaly and high WBC counts, were significantly associated with shorter survival. By multivariate analysis, only marrow blasts >10% and palpable splenomegaly had prognostic impact on survival. Although promising, the efficacy of azacitidine in advanced CMML needs to be confirmed in a randomized prospective study. © 2013 Elsevier Ltd.
Prebet T.,Johns Hopkins University |
Prebet T.,Institute Paoli Calmettes |
Gore S.D.,Johns Hopkins University |
Esterni B.,Institute Paoli Calmettes |
And 11 more authors.
Journal of Clinical Oncology | Year: 2011
Purpose: Azacitidine (AZA) is the current standard of care for high-risk (ie, International Prognostic Scoring System high or intermediate 2) myelodysplastic syndrome (MDS), but most patients will experience primary or secondary treatment failure. The outcome of these patients has not yet been described. Patients and Methods: Overall, 435 patients with high-risk MDS and former refractory anemia with excess blasts in transformation (RAEB-T) were evaluated for outcome after AZA failure. The cohort of patients included four data sets (ie, AZA001, J9950, and J0443 trials and the French compassionate use program). Results: The median follow-up after AZA failure was 15 months. The median overall survival was 5.6 months, and the 2-year survival probability was 15%. Increasing age, male sex, high-risk cytogenetics, higher bone marrow blast count, and the absence of prior hematologic response to AZA were associated with significantly worse survival in multivariate analysis. Data on treatment administered after AZA failure were available for 270 patients. Allogeneic stem-cell transplantation and investigational agents were associated with a better outcome when compared with conventional clinical care. Conclusion: Outcome after AZA failure is poor. Our results should serve as a basis for designing second-line clinical trials in this population. © 2011 by American Society of Clinical Oncology.
Treatment with lenalidomide does not appear to increase the risk of progression in lower risk myelodysplastic syndromes with 5q deletion. A comparative analysis by the Groupe Francophone des Myelodysplasies
Ades L.,Groupe Francophone des Myelodysplasies |
Le Bras F.,Groupe Francophone des Myelodysplasies |
Sebert M.,Groupe Francophone des Myelodysplasies |
Kelaidi C.,Groupe Francophone des Myelodysplasies |
And 16 more authors.
Haematologica | Year: 2012
Background: Although lenalidomide is very effective in the treatment of anemia of lower risk myelodys plastic syndromes with 5q deletion (del 5q), concerns have been raised over the fact that this drug could trigger progression to acute myeloid leukemia in some patients. Design and Methods: Ninety-five transfusion-dependent patients with lower risk myelodysplastic syndromes with del 5q were treated with lenalidomide (10 mg/day, for 3 weeks every 4 weeks); six (6.3%) of the patients progressed to acute myeloid leukemia. This cohort of 95 lenalidomide-treated patients was compared to a historical control cohort of 99 patients with lower risk myelodys-plastic syndromes with del 5q who never received lenalidomide, using a propensity score approach that can control for potential confounders in non-randomized comparisons. Results: The 4-year estimated cumulative incidence of leukemia was 9% in patients treated with lenalidomide and 15.8% in controls who did not receive lenalidomide (P=0.16). Conclusions: Using a propensity score approach, we found no significant difference in acute myeloid leukemia progression and survival from diagnosis between the cohort treated with lenalido-mide and the control cohort. © 2012 Ferrata Storti Foundation.
PubMed | Groupe Francophone des Myelodysplasies
Type: Clinical Trial | Journal: Leukemia research | Year: 2013
The effect of azacitidine (AZA) in therapy related MDS and AML (t-MDS/AML) is not well established. 54 patients (42 t-MDS and 12 t-AML), 71% of whom had complex karyotype, received AZA for at least one cycle (median 4 cycles). The overall response rate (ORR) was 39% in the whole cohort and 62% in patients who received 4 cycles. One, 2 and 3 year OS was 36%, 14% and 8% respectively. Female gender (p=0.01) and ECOG 0-1 (p=0.04) were associated with significantly better OS, while karyotype and marrow blast percentage had no significant impact. By comparison with de novo MDS/AML treated in the same program, t-MDS/AML had a similar response rate (38% vs 45% in de novo MDS/AML, p=0.53), but significantly shorter OS (2 year OS of 14% vs 33.9%, p=0.0005). However, in a multivariate analysis performed in all patients (de novo and therapy related cases), only complex karyotype and high IPSS, and not etiology (i.e. de novo versus therapy related), had a significant impact on OS. Nine (15%) patients received allogeneic stem cell transplantation, 4 of whom were still alive.
PubMed | Groupe Francophone des Myelodysplasies, NICHE and University Paris Diderot
Type: Journal Article | Journal: Mediterranean journal of hematology and infectious diseases | Year: 2015
The 2008 WHO classification identified refractory cytopenia with unilineage dysplasia (RCUD) as a composite entity encompassing refractory anemia, refractory thrombocytopenia (RT), and refractory neutropenia (RN), characterized by 10% or more dysplastic cells in the bone marrow respective lineage. The diagnosis of RT and RN is complicated by several factors. Diagnosing RT first requires exclusion of familial thrombocytopenia, chronic auto-immune thrombocytopenia, concomitant medications, viral infections, or hypersplenism. Diagnosis of RN should also be made after ruling out differential diagnoses such as ethnic or familial neutropenia, as well as acquired, drug-induced, infection-related or malignancy-related neutropenia. An accurate quantification of dysplasia should be performed in order to distinguish RT or RN from the provisional entity named idiopathic cytopenia of unknown significance (ICUS). Cytogenetic analysis, and possibly in the future somatic mutation analysis (of genes most frequently mutated in MDS), and flow cytometry analysis aberrant antigen expression on myeloid cells may help in this differential diagnosis. Importantly, we and others found that, while isolated neutropenia and thrombocytopenia are not rare in MDS, those patients can generally be classified (according to WHO 2008 classification) as refractory cytopenia with multilineage dysplasia or refractory anemia with excess blasts, while RT and RN (according to WHO 2008) are quite rare. These results suggest in particular that identification of RT and RN as distinct entities could be reconsidered in future WHO classification updates.
News Article | November 18, 2016
The Report “Myelodysplastic Syndrome - Market Insights, Epidemiology and Market Forecast-2023” Reports provides an overview of the disease and global market trends of the Crohn’s disease for the seven major markets ie: United States, EU5 (France, Germany, Italy, Spain, UK) and Japan. The Report covers the therapeutics market revenue; average cost of therapy, treatment practice and Myelodysplastic Syndrome forecasted market share for ten years to 2023 segmented by seven major markets. In addition, the report also includes global forecast of epidemiology of Myelodysplastic Syndrome till 2023. Key Companies covered in this report Celgene Corporation, Novartis AG, Sanofi, Johnson & Johnson, Merck & Co. Inc., Pfizer Inc., Onconova Therapeutics Inc., Groupe Francophone des Myelodysplasies, Amgen Inc., Eisai Co. Ltd. etc. Get SAMPLE of Report Spread across 100 pages with 20 Figures Now available at http://www.reportsnreports.com/contacts/requestsample.aspx?name=669380