MDS-391: Role of Erythropoiesis-Stimulating Agents (ESAs) in Supportive Care of Low-Risk Myelodysplastic Syndromes

Context: Erythropoiesis-stimulating agents (ESAs) are the frontline treatment in low-risk anemic MDS patients, and employment of this therapy in the earlier stage of the disease can delay the need for RBC transfusion, hypothetically by slowing the disease course. It is a matter of debate whether the clinical response is a result of proliferation and maturation of the dysplastic clone or stimulation of residual normal erythropoiesis by ESAs. Objective: Macrocytosis is one of the cytological hallmarks of dyserithropoiesis in MDS. An analysis of the erythropoietic response to ESA therapy in a cohort of anemic, non-transfusion-dependent MDS patient, enrolled in a retrospective registry, RECAMDS, a subgroup of Italian register, was performed. Design: Real-world analysis. Setting: Low-risk MDS. Patients: One hundred eighty-three patients treated with standard-dose ESAs have been retrospectively analyzed. Data analysis was performed according to IWG 2006 criteria at baseline and after 3 and 6 months of continuous treatment, with a sub-analysis of the patients according to WHO and R-IPSS risk stratification. ESAs were started at mean Hb concentration of 9.31 g/dl and mean serum EPO concentration of 51 mU/L after a mean time from diagnosis of 6 months (r.1–118). Interventions: ESAs to manage low-risk MDS. Main outcome measures: Results were evaluated according to IMWG 2006 criteria. Results: ORR was 83.6% (153/183); no difference among WHO and IPSS subgroups was found: 132/183 (72.1%) achieved response after 3 months of treatment, while the other 21/183 (11.2%) achieved response after 6 months. Nineteen patients with stable disease (non-responders, according to IWG criteria), in whom treatment was continued, achieved response after 9 months. In the macrocytic-responders group, 83.2% exhibited repeat macrocytosis after 3 months, while 16.8% became normocytic. In the normocytic-responders group, 89.8% exhibited repeat normocytosis, while 10.2% become macrocytic: in these patients, after 3 months, there was a contemporary worsening in neutropenia and thrombocytopenia with transfusion-dependence, which was regarded as first signs of progression of disease. Non-responders were 30/183 (16.3%): in the macrocytic non-responders group, 89% exhibit macrocytosis again after 3 months, while 11% became normocytic; in the normocytic group, 76% exhibited macrocytosis again, while 24% became normocytic. Conclusions: These preliminary data can suggest that, in the majority of MDS patients responsive to ESAs, the increase of Hb concentration occurs, mainly stimulation of erythroid production in MDS clones. In the minority of patients, it likely happens due to recruiting residual polyclonal erythropoiesis. It is interesting to note that stimulating effects of ESAs last, even when the expression of dysplasia progresses.