Results of a Multicenter Treatment Survey Yielding Insights Into Diagnosis and Management of MDS Patients In Daily Clinical Practice In Germany
Authors: Gattermann Norbert , Kuendgen Andrea , Kellermann Lenka , Zeffel Matti , Berger Hans-Juergen , Germing Ulrich 
Published: October 2019

Abstract
Abstract 4959
During the last few years (yrs) remarkable improvements have been made in the treatment of patients (pts) with myelodysplastic syndromes (MDS). However, there are only few analyses available on daily clinical practice, in particular on how pts are managed in the era of hypomethylating agents. For the first time, this analysis offers a comprehensive insight into diagnosis and management of MDS in Germany. Prior to patient documentation, 117 of 886 centers contacted provided information on patient load in a structural evaluation; the data collection period was scheduled accordingly. The data for this retrospective, non-interventional analysis were gathered during the 3rd and 4th quarter of 2009. 57 representative institutions documented 303 pts (41% from private-based offices [PBO], 59% from hospitals), 269 of which met the inclusion criteria (treatment decision, i.e. start, change or discontinuation, during data collection period; pts fully documented; positive plausibility check of data) of this analysis. Median age at the time of first diagnosis was 70 yrs. 78% had a Karnofsky Index (KI) ≥ 80%. The most common symptoms leading to diagnosis included cytopenia (e.g. anemia 79%), fatigue (38%), and deteriorating performance (36%). Distribution among MDS types according to the FAB classification at the time of first diagnosis was: 32% RA, 16% RARS, 20% RAEB, 4% RAEB-T, 7% CMML (21% “not documented”). According to WHO classification (2008), the distribution was: 17% RCUD, 12% RARS, 23% RCMD, 13% RAEB-I, 15% RAEB-II, 1% MDS-U, 5% MDS with del5q, 14% unknown/not classified as MDS. Cytogenetic analysis was performed in 67% of pts at initial diagnosis, but much less frequently (44%) in pts > 75 yrs (p<0.001; see table). The proportion of pts karyotyped was higher in university hospitals (83%) than non-university hospitals (63%) and PBOs (58%). Accordingly, more pts had their prognosis assessed by IPSS in university hospitals (75%) than non-university hospitals (61%) and PBOs (48%) (p=0.01). Red blood cell transfusions (RBCT) were given more often in non-university hospitals (30%) than university hospitals (10%) or PBOs (23%) prior to first diagnosis. The percentage of pts receiving RBCT was lower among older pts (> 70 yrs). However, length of transfusion history and frequency of RBCT were higher in older pts. The IPSS score was calculated in 61% of all pts at diagnosis. IPSS score calculation depended on several factors, e.g. RBCT dependence prior to diagnosis, age, and WHO MDS type. On bivariate analysis, IPSS scoring at first diagnosis was done significantly less frequently in pts > 75yrs (p=0.014; see table) and significantly more frequently in pts belonging to WHO types RCUD, MDS del(5q) and RAEB I-II (p<0.001). The IPSS score was more regularly used in university hospitals than other institutions (p=0.001). On multivariate analysis, the WHO type of MDS was confirmed to be the most relevant predictor of physicians using the IPSS (p<0.001). When trying to identify factors driving active treatment (defined as chemotherapy, stem cell transplantation (SCT), immunosuppressants, hypomethylating or other novel agents) in this survey, bivariate analysis showed a significant correlation with age ≤ 75 yrs (p=0.007) and the WHO types of RCUD, MDS del(5q), and RAEB I-II (p=0.0019); multivariate analysis revealed age as the most important factor (p=0.006; see table). MDS initial treatment was as follows: Supportive care only (34%), G-CSF/ESA only (16%), azacitidine (19%), any other active treatment (27%), and allogeneic SCT (5%). Azacitidine was the active treatment most frequently used (44 % overall) in MDS pts.Table:Impact of age on MDS diagnosis and treatmentPts ≤ 75yrsPts >75yrsSignificance% of pts with cytogenetic analysis performed at first diagnosis72.9%43.7%p<0.001% of pts with assessment of IPSS score65.4%51.0%p=0.014% of pts receiving active treatment39.7%22.2%p=0.006

Conclusion:
While distribution among prognostic groups in this survey was consistent with previous findings from the Duesseldorf MDS Registry, it became clear that many patients, particularly the older ones, did not receive a comprehensive risk assessment including cytogenetics/IPSS. Proper risk assessment, however, is important for correct and consistent therapeutic decision-making, particularly with the availability of treatment options that offer a significant survival benefit to defined groups of patients.

Disclosures:
Gattermann: Novartis, Celgene: Honoraria, Research Funding. Kuendgen: Celgene: Honoraria. Zeffel: Celgene: Employment. Berger: Celgene: Employment. Germing: Celgene, Chugai, Novartis, Amgen: Honoraria; Celgene, Novartis, Amgen, GSK: Research Funding.