Myelodysplastic Syndrome (MDS) represents a heterogeneous group of myeloid neoplasms, resulting in progressive bone marrow failure and cytopenias. Although the allogeneic hematopoietic stem cell transplantation (HSCT) is the only potential curative treatment, only few patients are candidates. In this regard, hypomethylating agents (HMA)- Azacitidine (AZA) and decitabine (DEC) - appears as a standard treatment for higher-risk MDS, in addition to being considered in oligoblastic acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML). Although AZA improved the overall survival (OS) in clinical trials, results in real-world are discordant. This study aims to evaluate the clinical characteristics and outcomes of MDS patients treated with HMA in an academic hospital.

Retrospective cohort, over 18 years of age, diagnosed with MDS, oligoblastic AML and CMML, de novo or secondary, treated with HMA and followed up at the cytopenias outpatient clinic at HCFMUSP from 2010 to June 2021. Data were collected from medical records and stored in REDcap. IWG 2006 criteria were used for response assessment. Kaplan-Meier curves were used for survival graphs, and Cox model regression for uni and multivariate analysis.

70 patients, 60 (85%) treated with AZA and 10 (15%) with DEC. Median age at diagnosis was 60.9 years (IQR 48.7 – 68.3), 61.4% male. In relation to diagnoses, 28 had de novo MDS (32.9% with excess of blasts; 4.3% with multilineage dysplasia; 2.9% with ring sideroblasts); 7 had AML (10%); 24 secondary myeloid neoplasm (21.4% therapy related; 7.1% with germline/ Fanconi predisposition; 5.7% after acquired aplastic anemia). The median score of IPSS and IPSS-R was respectively 1.5 and 6.0 (high risk). Before treatment 35.4% of patients had poor or very-poor karyotype. Response evaluation was assessed in 51 patients (72.8%) at the end of fourth cycle. The overall response rate (ORR) was 66.6%, including complete, partial and marrow responses, besides hematological improvement. Twelve patients (17%) undergone HSTC. The median OS, since starting HMA, was 11.5 months (IQR 8.1 – 13.8 95% CI), with median follow-up of 15.9. In univariate analysis, variables associated with worse OS were late initiation of HMA (HR 2.39 95% CI 1.18 – 4.84, p =0.015), age (HR 1.03 95% CI 1.01 – 1.05, p =0.007), poor-risk karyotype (HR 4.8 95% CI 2.29 – 10, p <0.001), hemoglobin < 8.5 (HR 3.44 95% CI 1.56 – 7.88, p =0.002) and platelets < 80.000 (HR 3.5 95% CI 1.49 – 8.23, p =0.002). In multivariate analysis, parameters associated with worse OS were transfusion dependency (HR 2.26 95% CI 1.27 – 4.04, p = 0.006) and poor karyotype (HR 2.53 95% CI 1.41 – 4.57, p =0.002). Thirty-five patients (50%) had febrile neutropenia, and 30% delayed one or more cycles.

The results reinforce the poor outcomes of higher-risk MDS despite the use of HMA. Some real-world studies previously published had already showed a suboptimal drug benefit, probably by the underutilization and low persistence of the treatment, in a subgroup of critically ill patients.

This retrospective analysis confirms the poor prognosis of higher-risk MDS treated with HMA. Poor-risk karyotype and transfusion dependency are the main factors that impact the outcomes.