Abstract
Introduction: Clinical course, prognosis, and therapy are heterogeneous in patients with myelodysplastic syndromes (MDS). Iron chelation, epigenetic treatment, lenalidomide, and allogeneic stem cell transplantation are the only approved therapies. As these treatments are successful only in a minority of patients, other approaches, which do not always meet the criteria of evidence-based medicine, are also used in an individualized manner.
In order to get a comprehensive picture of MDS treatment we analysed 1021 patients who were treated between 2007 and 2013. We included patients with RAEB-T (5%) and CMML (10%). Treatment regimens were inititated at our department.
Methods: Diagnoses were established within the Düsseldorf MDS Registry. All treatments were documented until 31 Dec 2013. Prognostic risk assessment was performed according to the International Prognostic Scoring System (IPSS) and its revised version (IPSS-R).
Results: Median age was 68 years (18-93 years), 13.5 % of patients were >80 years of age. 41% were diagnosed as RCMD, 12% as RAEB I, 15% as RAEB II, 4% as MDSdel(5q), 5% as RARS, and 9% as RCUD. Anemia was present at first diagnosis in 62.5%, hemorrhagic diathesis in 10%, and at least one comorbidity in 51%.
Transfusion therapy was the only treatment in 57% of the patients. 43% (n=441) received at least one specific treatment during the course of the disease. The median number of different therapies was 2 (range 1-9). Of these, 29.9% received cytokines (Epo, G-CSF), 14.4% iron chelation, 11.0% immunomodulation (lenalidomide, thalidomide), 8.7% immunosuppressive treatment (ATG, CSA, AntiCD52), 16.4% cytoreduction (Ara-C, hydroxyurea), and 16.4% valproic acid as a histone-deacetylating agent (HDAC), partly in combination with all-trans retinoic acid. 28.3% were treated with hypomethylating agents (5-azacytidine, decitabine), 14.6% with induction chemotherapy, and 31.1% underwent allogeneic stem cell transplantation. 5,2 % of the patients were treated within clinical trials.
Treatment approaches were distributed among IPSS risk groups as follows: cytokines (low: 55.6%/ intermediate-1: 32.8% /intermediate-2: 24.1%/ high: 9.1%), chelation (18.1%/20.9%/8.9%/4.5%), epigenetic treatment (HMA) (6.9%/19.4%/48.1%/54.5%), immunmodulation (19.4%/13.4%/7.6%/2.3%), immunosuppressive treatment (5.6%/17.2%/2.5%/0.0%), HDA (26.4%/16.4% /11.4%/13.6%), induction chemotherapy (5.6%/9.7%/20.3%/34.1%), cyto-reduction (9.7%/13.4%/20.3%/13.6%), and allogeneic stem cell transplantation (13.9%/32.8%/48.1%/54.5%).
Using the IPSS-R, results were similar: cytokines (very low: 62.5%/low: 38.0%/intermediate:25.3%/high: 29.6%/very high:11.5%), chelation (15.6%/26.0%/10.1%/14.8%/5.8%), epigenetic treatment (HMA)(6.3%/8.0%/ 30.4%/40.7%/44.2%), immunmodulation (9.4%/18.0%/7.6%/7.4%/5.8%), immunosuppression (9.4%/11.0%/16.5%/3.7%/3.8%), HDA (21.9%/26.0% /13.9 %/11.1%/15.4%), induction chemotherapy (6.3%/7.0%/17.7%/20.4%/26.9%), cytoreduction (12.5%/11.0%/20.3%/14.8%/15.4%) and allogeneic transplan-tation (15.6%/22.0%/36.7%/48.1%/50.0%).
More than 96% of the patients who were treated with HMA, induction chemotherapy or allogeneic transplantation had high-risk MDS (at least IPSS intermediate II) either at diagnosis or during the course of the disease.
Conclusions: Our survey shows that off-label treatment is frequent in MDS because there is still a lack of efficient therapies for many patients. During the observation period several treatment modalities were employed, varying in number and type according to IPSS and IPSS-R risk groups.Although numerous clinical trials with new compounds were initiated over the last few years, only a minority of MDS patients were eligible to participate. In the future, a further increase in clinical trial activity will hopefully allow a greater proportion of MDS patients to get access to effective treatment.
Disclosures
Xicoy: Celgene: Honoraria. Kuendgen:Celgene: Honoraria, Research Funding. Kobbe:Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Medac: Other; Astellas: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Neovii: Other. Gattermann:Novartis: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding. Germing:Novartis: Research Funding; Celgene: Honoraria, Research Funding; AMGEN: Research Funding; Janssen-Cilag: Honoraria, Research Funding; Boehringer-Ingelheim: Honoraria.
Precision Medicine at Work: Genetic Profiling to Guide Stem-Cell Transplantation in Myelodysplastic Syndromes