Outcome of Low Dose Azacitidine in Patients of Lower Risk Myelodysplastic Syndromes
Authors: Ghosh Kaustav , Dolai Tuphan Kanti , Mandal Prakas Kumar , Jena Rabindra 
Published: December 2024

Introduction: Myelodysplastic syndromes (MDS) are clonal haematopoietic stem cell disorders characterised by dysplasia leading to cytopenias and a high probability of progression to acute myeloid leukaemia (AML). In 2004, the US Food and Drug Administration approved the hypomethylating drug azacitidine for the treatment of MDS. Most strategies in lower-risk MDS (LR-MDS) have focused on improving transfusion requirements or are only active in a small subset of patients. Given the poor prognosis of a fraction of LR-MDS patients, strategies that could alter the natural history and improve overall survival are needed.
Materials and Methods: This was a prospective observational study of 20 LR-MDS cases over a study period of 18 months in the Department of Hematology, Nil Ratan Sircar Medical College and Hospital, Kolkata, India. All patients received subcutaneous azacitidine at 75 mg/m2 for three days in every four weeks for six cycles and were followed up for another six months. Primary specific objective of the study was to assess the overall response (complete response, partial response, marrow complete response, hematological improvement, stable disease, failure), and secondary specific objectives were to assess transfusion dependency, overall survival, and ECOG performance status.
Results: The median age was 53.5 years, with 65% (n = 13) of the study population being in the 41-60 years age group. Male: female ratio 1.85:1.
As per WHO 2016 classification, six patients (30%) had MDS-SLD (single lineage dysplasia), 11 patients (55%) had MDS-MLD (multilineage dysplasia), two patients (10%) had MDS-RS-SLD (ring sideroblast-single lineage dysplasia), and one patient (5%) had MDS-EB1 (excess blasts 1).
Five patients (25%) were in the low-risk, and 15 patients (75%) were in the intermediate-risk IPSS-R category. Good cytogenetics was present in 16 patients (80%), and four patients had intermediate cytogenetics (20%). Normal cytogenetics was present in 60% of patients, followed by Del 12q in 15% of patients. Del 7q and Gain 8 were each present in 10% of patients. One patient had Del 20q (5%).
At the end of the study period, 11 patients (55%) showed an overall response. Four patients (20%) showed a complete remission, three patients (15%) showed partial remission, four patients (20%) showed marrow complete remission, and 11 patients (55%) showed hematological improvement.
By using the paired t test, it was found that the mean deviation rise of hemoglobin (1.52 g/dl) and absolute neutrophil count (630.55/cmm) at 6 months was higher compared to baseline (P value ≤ 0.05).
By using an independent T test, it was observed that a better overall response was achieved among patients with a higher baseline platelet count (mean ± standard deviation = 157000 ± 104035.57) (P value ≤ 0.05).
Coming to ECOG performance status, 62.5% of the patients had improvement in ECOG status after six cycles of low-dose azacitidine.
At baseline, 18 patients with LR-MDS (90%) were transfusion dependent. After 6 cycles of low-dose azacitidine therapy, 10 out of 18 patients (55.6%) were transfusion-independent. Myelosuppression and infections were observed in 35% and 25% of the patients, respectively.
One-year overall survival was 95% (n = 19). The Kaplan-Meier curve for survival analysis was done with a single intervention, which showed one death at 8 months (due to intracerebral hemorrhage) among 20 participants. Estimated mean survival time was 11.8 months.
Conclusions: Azacitidine can be a cost-effective treatment for transfusion-dependent LR-MDS, particularly in an emerging market and mid-income economic country like India. An overall response and one-year overall survival were achieved in 55% and 95% of the patients, respectively. Transfusion independence and improvement in ECOG performance status were achieved in 55% and 62.5% of the patients, respectively, at the end of the study period. Azacitidine is a safe drug with only minor adverse effects. The present study had a couple of limitations. The current study included only a limited number of patients, and six cycles of azacitidine were given in this study with short-term follow-up. Studies with a larger number of patients and a longer duration of follow-up are required to understand the effectiveness and duration of low-dose azacitidine in patients of LR-MDS patients to achieve a sustainable overall response.