Overall Survival and Erythroid Response in Patients with Low-Risk Myelodysplastic Neoplasms after First-Line Treatment in a Low-Middle Income Country

Introduction

Myelodysplastic neoplasms/syndromes (MDS) are a heterogeneous group of clonal disorders characterized by ineffective hematopoiesis and an increased risk of transformation to acute myeloid leukemia (AML). Current standard risk stratification model, the Revised International Prognostic Scoring System (IPSS-R), classifies patients into lower (≤3.5 points) or higher risk MDS. Lower-risk MDS (LR-MDS) treatment is based on the prevailing cytopenia and intends to improve symptomatic burden and minimize transfusion dependency.

Anemia is present in 80-90% of patients with MDS. Throughout most of the course of the disease, patients with MDS have a hemoglobin < 10 g/dL, which leads to a decreased quality of life. Also, 50% of patients with MDS will eventually need red blood cell transfusions. Current options for the active treatment of anemia in LR-MDS are limited and vary among countries. Although erythropoiesis stimulating agents (ESAs) are considered standard of care in the absence of del5q, immunosuppressive therapy (IST) and androgens are still used in low income countries. The present study aims to evaluate whether erythroid responses and overall survival differ in patients with LR-MDS, based on their first-line treatment.

Methods

This is a retrospective study in patients with LR-MDS at Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, a tertiary care center in Mexico City. Eligible patients were diagnosed between January 2002 and December 2022 according to World Health Organization (WHO) 2016 criteria. Response was assessed according to International Working Group (IWG) 2018 criteria. We defined erythroid response (HI-E) as the sum of the responses achieved within different transfusion burden categories.

First line therapy included ESAs, IST (cyclosporine ± eltrombopag), and androgens (mesterolone, danazol). These were compared through bivariate analysis, Kaplan-Meier curves and log-rank test.

Results

Until December 2022, 109 LR-MDS patients were considered for inclusion. Among them, 29 patients were lost to follow-up, and 25 patients were solely observed without any further therapy. Also, 7 patients who received other therapies were excluded. Ultimately, 48 patients were included in this analysis, 56.3% (n=27) were female, mean age was 62.8 (±15.9) years. Based on WHO 2016 classification, MDS with uni- and multilineage dysplasia was present in 58.3% (n=28) of the patients, while 29.2% (n=14) had hypoplastic MDS. Anemia was present in 89.6% (n=43) of the patients. When evaluating transfusion burden, 37.5% (n=18) of patients were non-transfusion dependent (NTD), 31.3% (n=15) low-transfusion burden (LTB), and another 31.3% (n=15) high-transfusion burden (HTB). ESAs and IST were the most frequently used frontline therapies, each accounting for 41.7% (n=20) of the patients; the remaining 16% (n= 8) received androgens. When comparing baseline characteristics between treatment arms, we found lower hemoglobin values and a greater proportion of severe anemia in ESA-treated patients (p= 0.039, p= 0.036), however, no differences in transfusion burden was observed (p= 0.212).

Erythroid response rates were 25% (n=5), 20% (n=4) and 62.5% (n=5) among those treated with ESAs, IST and androgens, respectively (p= 0.071). When assessing HI-E by transfusion burden, no differences were observed between treatment arms except in HTB patients (p= 0.023). Neither time to response, nor duration of response were significantly different between treatment groups ( Table 1). Importantly, 3 of the 4 responders in the IST group received cyclosporine monotherapy, also 50% were hypoplastic MDS.

After a median follow up of 47 months (IQR:22.5-85.5), the median overall survival(OS) for the entire cohort was not reached. The 3-year-OS rates for IST, ESA and androgens were 94%, 54% and 50%, respectively (p= 0.018) ( Figure 1).

Conclusions

In spite of the bias and limitations in the retrospective nature of this study, IST seems to be a valid option in frontline therapy for LR-MDS, since HI-E rates are similar to those observed with ESAs. Additionally, IST group showed a better OS. Results obtained with androgens merit further study and should be interpreted with caution because of the sample size.