Detection and Treatment of Iron Overload in Red Blood Cell (RBC) Transfusion-Dependent Myelodysplastic Syndromes (MDS): A European Survey.
Authors: Giagounidis Aristoteles , Heptinstall Kathy , Jasmin Didì , Leto di Priolo Susanna , Ille Susanne , Fenaux Pierre 
Published: October 2019

Abstract
Abstract 4830

Background
Repeated RBC transfusions in patients with MDS cause progressive iron accumulation in the liver, heart and endocrine glands, with potentially deleterious effects on those organs. Iron chelation therapy (ICT) has been shown to ameliorate the toxicity of iron overload in patients with thalassemia. Although the clinical consequences of iron overload and effects of ICT have not been as well demonstrated in patients with MDS, country-specific guidelines for monitoring and treating iron overload have been published. To gain a better understanding of the detection and management of iron overload in Europe, the MDS Iron-overload Detection Insight Survey (MIDIS) was conducted in European physicians treating transfusion-dependent patients with MDS. The MIDIS was conducted by the MDS Foundation and the European School of Haematology in partnership with Novartis Oncology.

Methods
European physicians who were seeing at least one transfusion-dependent patient with MDS in an average 6-month period were invited to take part in the survey. The 15-minute questionnaire was web- or paper-based and comprised a number of closed- and open-ended questions.

Results
338 physicians from 27 European countries participated in the survey. Respondents had a mean age of 44 years (54% M, 46% F), a mean of 18 years' experience, and were fully qualified (87%) or in training (13%). 59% worked at teaching hospitals, 28% in general hospitals and 13% in other institutions. Respondents saw a mean of 19 RBC transfusion-dependent patients with MDS per 6 months. 46% and 27% of respondents noted that detection of iron overload in transfusion-dependent MDS was ‘very important’ or ‘important’, respectively. 53% replied that they monitored serum ferritin levels in those patients quarterly, while 26% said that how often they monitored depended on the frequency of transfusions. Respondents said that serum ferritin always (46%) or sometimes (47%) had an impact on treatment decisions. The main barriers to detecting iron overload were: poor patient prognosis (relevant barrier in 30% of respondents); low frequency of serum ferritin monitoring (30%); and lack of awareness about guidelines (27%) and about the risks of iron overload (23%). Other barriers were: a low priority for iron-overload screening (23%); and perceptions about the importance of iron overload in MDS (17%). Factors that positively influenced detection of iron overload included: >20 RBC units received (relevant trigger in 76% of respondents); introduction of serum ferritin as a standard test (76%); and awareness of the potential risks of frequent transfusions (75%). 37% and 31% of respondents believed that treating iron overload in RBC transfusion-dependent patients with MDS was ‘very important’ or ‘important’, respectively. 90% of physicians prescribed ICT in those patients; however, a mean of only 38% of patients received ICT. Factors leading respondents to initiate ICT included: patient age of 55–64 years (important in 77% of respondents); serum ferritin levels of >1000 ng/mL (76%); candidacy for allogeneic SCT (76%); need to prevent organ dysfunction (74%); ≥2 RBC units transfused per month (71%); lifetime transfusions of >20 RBC units (68%); and convenience of oral ICT (67%). The barriers to initiating ICT mostly related to poor patient prognosis (72%) and patient age ≥85 years (50%), while others included: comorbidities limiting prognosis (34%), including renal problems (27%); Int-2 or High IPSS-risk MDS (31%); and expected non-compliance (28%). There were differing opinions regarding the importance of some of the barriers to initiating ICT; 31% of respondents said that a high-risk classification and 28% said expected non-compliance were high barriers, while 25% and 23%, respectively, thought that these were weak barriers.

Conclusions
Most respondents were experienced European physicians with a keen interest in MDS. 73% and 68% of physicians said they believe that detecting and treating iron overload, respectively, were ‘important’ or ‘very important’ in transfusion-dependent patients with MDS. In total, 90% of them prescribed ICT to their transfused patients with MDS. This survey showed that older age and poor patient prognosis (especially based on IPSS classification) were the greatest barriers to initiating ICT; however, the patient's physiological condition was also an important barrier.

Disclosures
Giagounidis: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Johnson & Johnson: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Heptinstall:The MDS Foundation: The MDS Foundation is a 501(c)3 patient advocacy organization. We receive grants from companies, individuals and groups but have no contractual obligation to any of these donors, and our research or advocacy decisions are independent. Jasmin:European School of Haematology: Employment; The European School of Haematology receives unrestricted educational grants from Novartis Pharmaceuticals: Research Funding. Leto di Priolo:Novartis Farma S.p.A.: Employment, Equity Ownership. Ille:GfK SE, a market research agency that has been commissioned and paid by Novartis Oncology to conduct the MIDIS survey data collection: Employment. Fenaux:Celgene: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Ortho Biotech: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Cephalon: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Novartis: Honoraria, Research Funding.