How Are Patients (Pts) with Lower-Risk Myelodysplastic Syndromes (MDS) Treated? Impact on Clinical Evolution and Overall Survival: A Report from the Erasme Study
Authors: Montoro Julia , Pomares Helena , Oiartzabal Itziar , Bernal Teresa , Barranco Edgardo , Coll Rosa , Romero Rafael , Calabuig Marisa , Salido Eduardo , Castellanos Marta , Medina Angeles , Azaceta Gemma , Navarro Mireya , López Silvia , Valcárcel David 
Published: November 2019

Abstract
Introduction: As MDS includes a wide range of heterogeneous neoplastic disorders, the therapeutic approaches for treatment of MDS vary greatly. The aim of this study was to evaluate the use of different therapies, and assess time from diagnosis to therapy initiation and pt outcomes, in an unselected Spanish population with MDS from the ERASME study.
Methods : The ERASME study (CEL-SMD-2012-01) is an observational, prospective, multicenter study of pts with either MDS or chronic myelomonocytic leukemia (CMML); disease was defined using the 2008 World Health Organization (WHO) classification system. Initial pt management strategy was classified into 3 groups: active therapy (AT), such as chemotherapy and treatment with azacitidine (AZA); allogeneic hematopoietic cell transplantation (HCT), which included pts receiving other therapies before transplantation; and observation and support (OB&SP), which included red blood cell (RBC) and platelet transfusions, and growth factors. Here, we present overall survival (OS) data from a prespecified interim analysis of pts with International Prognostic Scoring System (IPSS)-defined Low- and Intermediate-1-risk (lower-risk [LR]) MDS using the Kaplan-Meiermethod.
Results : A total of 207 IPSS-defined LR MDS pts (117 with Low-risk and 81 with Intermediate-1-risk MDS) were recruited from Jan 2013 to Feb 2014; median follow-up was 16.1 months (interquartile range [IQR] 11.5-19.1). Pt characteristics are described in the Table. We identified 14 pts with high-risk features (HRF) for MDS based on the presence of ≥ 1 of the following: neutropenia (n = 6; absolute neutrophil count < 0.5 × 109/L); thrombocytopenia (n = 4; platelet count < 50 × 109/L); grade 2-3 bone marrow fibrosis (n = 1); or adverse cytogenetic risk (n = 3). At baseline, 28 (14%) pts had RBC transfusion-dependence (RBC-TD), 166 (80%) were RBC transfusion-independent (RBC-TI), and 13 (6%) had missing data. Probability of RBC-TD increased over time with 41 of 166 pts having RBC-TD after 12 months. Median OS of RBC-TD versus RBC-TI pts was not reached (NR) (95% confidence interval [CI] 19.65 months-NR) versus NR (95% CI 22.93 months-NR), respectively (hazard ratio [HR] 3.2, 95% CI 1.13-9.22; P = 0.0275). At diagnosis, 117 (57%) pts (including 4 with HRF) were considered for OB, and 76 (37%) pts for SP (69 pts [5 HRF] for erythropoiesis-stimulating agents, and 7 pts [3 HRF] for RBC and platelet transfusions). Only 10 (5%) pts were considered for AT, which included AZA (n = 5; 1 HRF), lenalidomide (n = 4; 1 HRF), and alemtuzumab (n = 1). HCT was considered in 4 pts (2%; 3 with prior AZA treatment and 1 with prior chemotherapy). After 12 months, 13 (11%) of 117 OB pts switched to AT; median time to AT was 30 weeks (IQR 24.0-44.0). Of 76 pts receiving SP, 23 (30%) switched to AT; median time to AT was 23.9 weeks (IQR 16.3-39.1). Of 184 pts with Revised-IPSS (IPSS-R) scores, at 12 months' follow-up 35 had died (15 of 140 Very Low/Low-risk pts, 15 of 32 Intermediate-risk pts, and 5 of 12 High/Very High-risk pts). At 12 months, 36 of 207 (17%) LR MDS pts had died, including 6 of the 14 HRF pts. Median OS was shorter among HRF pts versus non-HRF pts (19.45 months [95% CI 5.52-NR] vs NR [95% CI NR-NR], respectively) (HR 3.5, 95% CI 1.47-8.53; P = 0.0048). Median OS for IPSS-R Very Low/Low-risk and Intermediate/High/Very High-risk pts was NR (95% CI NR-NR) and 19.45 months (95% CI 11.99-NR), respectively (HR 5.4, 95% CI 2.8-10.7; P < 0.001).
Conclusions : The typical treatment of LR MDS pts in Spain consists mainly of supportive care. We observed that risk of RBC-TD increased after diagnosis. These data suggest more attention should be provided at diagnosis or during follow-up of LR MDS pts with poor prognosis, and that they should be considered for more intensive treatment.
Abstract presented on behalf of the ERASME Study Investigators Group.

Disclosures
Off Label Use: Azacitidine was used in IPSS Intermediate-1-risk patients with MDS, and lenalidomide was used in MDS patients with del(5q) plus > 1 cytogenetic abnormality. Castellanos:SCLHH: Other: Membership; SEHH: Other: Membership. Navarro:Celgene Corporation: Employment. López:Celgene SL Unipersonal: Employment, Equity Ownership, Honoraria. Valcárcel:Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.