IMPACT of Therapeutic Strategy and Time to Therapy Initiation on Clinical Evolution in Higher-Risk Myelodysplastic Syndromes. a Report from Erasme Study
Authors: Montoro Julia , Coll Rosa , Valcarcel David , Tormo Mar , Calbacho Maria , Bernal Teresa , Fernandez Alfonso , Sanchez Joaquin , Albors Manuel , Arnan Montserrat , Barranco Edgardo , Rafel Montse , Garcia Regina 
Published: October 2019

Abstract
Introduction
The therapy of myelodysplastic syndromes (MDS) has undergone a dramatic change in the last years with the inclusion of the demethylating agents but data regarding their impact on the “real life” setting are still scarce. Moreover the time to therapy from diagnosis, that has been evaluated in acute myeloid leukemia has not formally been evaluated in the MDS. The aim of our study was to evaluate the use of the different therapies and the time to therapy in an unselected Spanish population within the ERASME study. Here we present data from a pre-specified interim analysis of MDS patients who fall into higher-risk categories (Group-2: int-2/high) included in the ERASME study.
Materials and methods
The ERASME study (CEL-SMD-2012-01) is an observational, post-authorization, prospective, multicenter study that will include a total of 600 patients with MDS and Chronic myelomonocytic leukemia (CMML) according to the World Health Organization 2008 classification and that follow them for at least three years (or until death). The primary objective of this study is to describe disease progression in routine clinical practice, based on the initial therapeutic strategy, in patients with newly diagnosed MDS and CMML.
The patients are classified in three groups: 1) low/Int-1 IPSS, 2) int-2/high and 3) CMML. Initial patient management strategy is classified in three groups: Observation (OB) & support (SP) (including blood and platelet transfusions and growth factors), active therapy (AT) (including chemotherapy, azacitidine, lenalidomide, etc) and allogenic hematopoietic cell transplant (HCT) (including those patients receiving other therapies before transplant). Initial data from the pre-specified interim analysis are presented.
Results
A total of 87 at int-2/high risk out of 254 MDS patients, 45% women with a median age of 73 years (range 39-87) were recruited between January 2013-June 2014. Of all patients, 57% had int-2 risk and 43% had high risk MDS. Median follow-up was 5.5 months (range 0-14.9). The most common MDS types were refractory anemia excess of blast type 1 and 2 (15% and 67%, respectively) and refractory cytopenia with multilineage dysplasia (16%). Cytogenetic abnormalities were present in 70% of patients (11% complex and 33% very complex Karyotype). Median bone marrow blast count was 12% (range 0-27). Hemoglobin, platelet, and neutrophil count was: 9.5 g/dL (range 6.7-13.3), 65x103/µL (9.7-439), and 1x109/L (range 0-24), respectively. In this patient population, the first therapeutic decision taken by the investigating physician was: AT in 49 (56%), HCT in 18 (21%) and OB&SP in 20 (23%) patients, each one. The main reason for treatment selection were risk-disease disease (94%), age (82%), symptomatology (66%) and comorbidities (55%). Patients in AT received azacitidine (n=44, 90%), chemotherapy plus azacitidine (n=4, 8%) and immunomodulatory therapy (n=1, 2%). Of those patients considered for HCT (n=18), 2 (11%) received transplant without prior therapy, and 16 (89%) received prior therapy with: azacitidine (n=10, 56%) chemotherapy (n=3, 17%), or both in (n=3, 17%). At last follow-up, 8 out of 18 HCT patients had undergone transplant within a median of 9.1 months (range 3.2-11) from diagnosis; 3 patients died before transplant, and 7 are still waiting for transplant. At last follow-up, a total of 26 (30%) have died: 11/6/9 patients for AT/HCT/OB&SP respectively (22%, 33%, 45%) (Log Rank, p= 0.1823). The overall survival was not reached (NR)/11.6/7.89 months (95% CI: 9.86-NR), (95% CI: 5.59-NR) and (95% CI: 2.17-NR), for each group, respectively. The median time from diagnosis to death in each group was 4.2, 4.8 and 2.2 months, respectively.
The median time between diagnosis and therapy for AT/HCT/OB&SP was 0.77/0.24/5.3 months (range 0.09-2.75), (range 0.03-2.79), (range 2.2-6.0), for each group, respectively.
Conclusions
Higher-risk MDS patients were treated on an individualized therapy strategy after diagnostic evaluation and prognosis assessment. Our prospective study confirms that azacitidine has become the most common therapy for higher-risk MDS patients, including most of HCT candidates.

Disclosures
Off Label Use: Vidaza, erythropoietin -stimulating agents, Revlimid. Valcarcel:Celgene: Honoraria, Speakers Bureau. Sanchez:Celgene: Consultancy, Speakers Bureau. Rafel:Celgene: Employment.