ALBERT

Description: INTRODUCTION Anemia is the most frequent cytopenia in lower-risk MDS. Erythropoietic-stimulating agents (ESAs) are commonly used in these patients. The use of ÒclassicalÓ parameters (EPO and ferritin levels) and the revised IPSS (IPSS-R) has been proposed1 (SantiniÕs score) to predict response to ESAs and overall survival (OS) among patients with lower risk MDS by IPSS and a favorable Nordic group score2. OBJECTIVES The main objective of the study was to evaluate overall response rate (ORR) to ESAs and OS according to the proposed SantiniÕs score in an independent and large cohort of anemic lower risk MDS patients receiving treatment with ESAs. METHODS Data from 530 anemic patients with low/int1 risk IPSS de novo MDS (according to FAB and WHO criteria) and sufficient follow-up data available were recorded in Spresas3 (SPanish Registry of Erythropoietic Stimulating Agents Study from GESMD). Two hundred and twenty six patients (42.6% of the patients) were selected according to specific criteria regarding the published SantiniÕs score1: Hb level 350 ng/mL(=1) and IPSS-R very low=0, low=1, intermediate=2 and high=3) yielded a score ranging from 0 to 5. ESAs response rate and overall survival were analysed according to these score. Response to treatment was evaluated according to IWG 2006 response criteria and a multivariate logistic regression analysis was used to identify independent predictors of erythroid response (ER). OS were defined as the time between diagnosis and the corresponding event or last follow up (Feb 2015) and were analyzed using univariable and multivariable Cox proportional hazards regression methods. RESULTS Median age was 77 years (interquartile range [IQR] 25%-75%: 71-83 y), median Hb level at start of treatment was 10 g/dL (IQR25-75: 9-10), median EPO level was 90 (IQR25-75: 27,25-108) and median ferritin level was 338,5 (IQR25-75: 146,5-568,75). Among 139 patients with this data available, 85 patients (61,1%) were RBC transfusion dependent before ESAs treatment. Median time from diagnosis to ESAs treatment was 82 (IQR25-75: 27-353) days. According to the IPSS, 68.6% (N=155) and 31.4% (N=71) were in low and Int-1 risk groups, respectively. Regarding IPSS-R, 23% (N=52), 66.8% (N=151), 9.7% (N=22) and 0.4% (N=1) were in very low, low, intermediate and high risk, respectively. ORR to ESA treatment was 71.2% (N=161), with a median duration of response of 2.06 years. Prognosis factors of ER showed a trend toward to a higher ER among patients in the lower IPSS-R (P〉0.05), low IPSS (p=0.039) and lower EPO levels (p

Description: 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.

Description: 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.