Report
Teaser, summary, work performed and final results
Periodic Reporting for period 2 - MDS-RIGHT (Providing the right care to the right patient with MyeloDysplastic Syndrome at the right time)
Teaser
Healthy ageing is one of the major challenges for the European community, as ageing introduces more health problems and healthcare utilisation. Both myelodysplastic syndromes (MDS) and anaemia, occurring more frequently in the elderly, limit quality of life (QoL) and increase...
Summary
Healthy ageing is one of the major challenges for the European community, as ageing introduces more health problems and healthcare utilisation. Both myelodysplastic syndromes (MDS) and anaemia, occurring more frequently in the elderly, limit quality of life (QoL) and increase the pressure on healthcare. MDS is a chronic bone marrow malignancy usually occurring in male patients aged 75 or older. Shortages in blood cells (cytopenias), leading to anaemia, infections and/or bleeding complications, are typical characteristics of MDS. The majority (75%) of patients with MDS are classified as lower-risk, which is associated with an 8-years loss of life expectancy compared to healthy elderly population. A considerable number of lower-risk MDS-patients (in total an estimated 2 million European citizens) remain ‘under diagnosed’ as anaemia of the elderly, due to insufficient awareness of the relevance of a right diagnosis and the reluctance to use bone marrow puncture (required for MDS diagnosis) in frail elderly, as this is often regarded too invasive and demanding. Consequently, these people do not have access to proper care. The MDS-RIGHT project aims to address the complex challenges associated with correct diagnosis and treatment of patients with MDS or anaemia of the elderly, using data from a comprehensive well-established European MDS Registry (EUMDS) and from a community-based Dutch population cohort (LifeLines). The main goal of the MDS-RIGHT project is to compare long-term outcomes and costs, as well as approaches to diagnose and to treat patients with MDS and anaemia of the elderly; to assess (epi)genetic abnormalities; and to develop more effective and safer evidence-based, tailored healthcare interventions (HCI) for lower-risk MDS or anaemia of the elderly, resulting in better treatment compliance and more cost-effective and safer use of HCI.
Healthcare for MDS is challenging and complex, as MDS is a heterogeneous disorder and most available HCI do not cure MDS, but generally aim to improve the bone marrow function and to restore the numbers of blood cells within all three different cell lineages (red blood cells, white blood cells and platelets). The EUMDS registry is ideally suited for comparing the effectiveness of currently available HCI for this predominantly elderly patient group and perfectly fits the topic PHC17-2014: ‘Comparing the effectiveness of existing HCI in the elderly’. The Registry hold longitudinal observational data from more than 2,381 lower-risk MDS patients with >10 years follow-up in 16 EU countries and Israel. Comparisons of this ‘real life’ data will help to identify the most cost-effective treatment strategies. MDS-RIGHT will facilitate development and validation of new, more effective diagnostic and prognostic procedures, enabling identification of specific patient groups more likely to benefit from HCI, contribute to more personalized care, improved evidence-based treatment guidelines, and more cost-effective use of resources. In order to achieve the above, MDS-RIGHT aims to address six objectives:
1 Comparing outcome and costs of existing HCI by using data from the comprehensive EUMDS Registry.
2 Enhancing compliance with diagnostic procedures in MDS, by introducing new diagnostic methods.
3 Maximising QoL by restricting MDS-specific HCI to patients with the right diagnosis, who are likely to benefit from these HCI.
4 Providing models that can better predict the likely response of a patient to a certain treatment, so called ‘treatment-outcome prediction models’, to support personalised decision making and robust economic analyses.
5 Developing improved, evidence-based diagnostic and therapeutic guidelines, based on the outcomes of objectives 1-4
6 Establishing a European MDS competence network encompassing all stakeholders for dissemination and utilization of up-to-date, evidence-based and regulatory guidance
Work performed
The MDS-RIGHT project is well on track. The impact of HCI on the established core outcome sets has been evaluated in several studies. We have shown that iron chelation clearly improved overall survival. Red blood cell transfusions are associated with an impaired progression-free survival and the negative impact of transfusions is already detectable at very low transfusion density (< 1 unit per month). Transfusion dependency is associated with a more rapid decline of QoL. Transfusions contain huge amounts of iron. Excess iron occurred exclusively in transfused patients and in patients with ring sideroblastic MDS, which is associated with increased iron resorption in the gut, and is associated with an impaired survival.
Usually bone marrow is necessary to monitor deterioration of MDS, but we showed that a rapid decline of platelets during the first 6 months after diagnosis is associated with impaired survival. This outcome may decrease the need for invasive bone marrow aspirates to monitor prognosis in MDS. Peripheral blood might be a representative source for molecular diagnosis of MDS. Therefore, we are assessing the occurrence of mutations in the blood of 650 normal individuals, who have anaemia without diagnosis of a haematological disorder. Mutational analysis has been performed in 1069 MDS patients. The mutational and epigenetic data will be integrated in the full dataset during the next period. These analyses will focus on 1. the identification of genetic lesions associated with independent prognostic value on overall survival, risk of disease progression, and risk of developing transfusion-dependency; 2. Integration of genetic lesions and clinical/haematological variables of prognostic value into prognostic scoring systems and 3. Recognition of genetic defects associated with response to the existing HCI and duration of response.
We compared QoL by EQ-5D-questionnaire at initial diagnosis in 1690 EUMDS patients with age- and sex-matched EuroQol Group norms. MDS patients experience a pronounced reduction in several distinct dimensions. In addition, we assessed QoL in 138.670 participants from LifeLines, showing that anaemic individuals older than 60 years experienced a significantly lower QoL than non-anaemic individuals.
The MDS-Europe multi-stakeholder website platform (www.mds-europe.eu), including the MDS-RIGHT project section (www.mds-right.org), has been extended and has a responsive format suitable for smartphone/iPad. The ‘News & events’, ‘Media centre’, and ‘Community’ sections and their subsections were added, and the ‘Resources’ section was further expanded with ‘Clinical Trials’, and ‘Registries’ subsections. The ‘Patient Management’ section, including the interactive tool for the new web-adapted recommendations, is currently being tested, and the first sections: ‘Diagnosis’ and ‘Prognosis’ are expected to become publically available on the MDS-Europe platform in 2018. ‘Treatment sections’ will follow in 2018/early 2019.
Final results
The activities within the MDS-RIGHT project are progressing quite well during the second reporting period. This progress will allow us to achieve the majority potential impacts as defined in our project.
Website & more info
More info: https://mds-right.eu/.