Prediction of Response to Erythropoiesis Stimulating Agents in Low-Risk Myelodysplastic Syndromes

Abstract

The natural history and prognosis of MDS are classified by the International Prognostic Scoring System (IPSS) and Revised International Prognostic Scoring System (R-IPSS). In low-risk MDS (low or intermediate-1 IPSS or R-IPSS ≤ 3.5), anemia is the predominant feature, often leading to red blood cell (RBC) transfusion requirement, poor quality of life, and worsening cardiovascular comorbidities (Steensma and Bennett, 2006). Correcting anemia by transfusion support or enhancing intrinsic

A Systematic Literature Review of Predictors of Erythropoiesis-Stimulating Agent Failure in Lower-Risk Myelodysplastic Syndromes

“…However, based on the quantitative associations with response, the general consensus followed that 'responders' had higher baseline hemoglobin levels than 'non-responders'. In four studies [26,36,39,52], this relationship was statistically significant, and in another four studies, it did not show statistical significance [30,45,46,50]. Moreover, in two other studies, 'responders' had lower median or mean hemoglobin levels than 'non-responders'; however, neither of these studies reported statistical significance [29,56].…”

“…However, the general consensus among them was that 'responders' had lower mean or median ferritin levels than 'non-responders'; in three studies [39,46,48], this relationship was statistically significant. In another three studies, it was not statistically significant [28,33,50]. Moreover, in one French study, 'responders' had higher median ferritin levels than 'non-responders' but did not report statistical significance [26].…”

“…Most studies were conducted in Europe (n = 24), and seven studies did not report the geographic location. Data sources were spread across nationwide registries, medical records in hospitals, Of the 38 studies identified (Table 2), one (3%) was a randomized controlled trial [22], three (8%) were non-randomized trials [23][24][25], 10 (26%) were single-arm trials [26][27][28][29][30][31][32][33][34][35], 15 (39%) were retrospective cohort studies [36][37][38][39][40][41][42][43][44][45][46][47][48][49][50], and four (11%) were prospective cohort studies [51][52][53][54]. One study (3%) was a compassionate, open-label, therapeutic trial [55], and four studies (11%) did not report the study design [56][57][58][59].…”

“…Studies varied in the response criteria used and the treatments given to patients. However, based on the quantitative associations with response, the general consensus followed that 'responders' had lower mean or median serum EPO levels than 'non-responders'; in 10 studies [26,30,33,36,40,48,50,53,55,59], this relationship was statistically significant while in four studies, it was not statistically significant [28,29,31,45]. The studies where no statistical significance was reported tended to be small (n ≤ 60), single-arm studies [28,29,31,45].…”

“…Three studies reported ORs of ≥2.4 with p values ≤ 0.001. One Canadian study reported its definition of transfusion dependence as needing ≥1 RBC transfusion every 8 weeks, over a period of 4 months; the other two studies did not provide a definition [41,42,50]. One study (country not reported) reported an HR of 2.867 (95% CI: 1.354-6.07; p = 0.006) [25].…”