ITACA: A new validated international erythropoietic stimulating agent-response score that further refines the predictive power of previous scoring systems.

BACKGROUND: In 'real-life', the Nordic score guides Erythropoietic stimulating agent (ESA) use in lower-risk myelodysplastic syndrome (MDS) with predicted response rates of 25% or 74%. As new treatments emerge, a more discriminating score is needed. OBJECTIVES: To validate existing ESA predictive scores and develop a new score that identifies non-responders. METHODS: ESA-treated patients were identified in 3 MDS registries in Italy and Canada (FISM 555, GROM 233, and MDS-CAN 208). Clinical and disease-related variables were captured. Nordic, MDS-CAN, and IPSS-R-based ESA scores were calculated and documented ESA responses compared. RESULTS: 996 ESA-treated patients were identified. Overall response rate (ORR) was 59%. The database was randomly divided into balanced derivation (n = 463) and validation (n = 462) cohorts. By multivariate analysis, transfusion independence, erythropoietin (EPO) level <100 IU/L, and IPSS low-risk were independently predictive of response. Assigning a score of 1 to each resulted in a scoring system of 0-3 with response rates of 23%, 43%, 67%, and 85%. ORR was concordant in the validation cohort. The 'ITACA' score had the highest discriminating power of response. CONCLUSION: ITACA is an internally-validated predictive SS of ESA response in real-life 'good risk' MDS patients derived from a large international dataset that surpasses others. The incorporation of biologic markers to better identify non-responders is still needed.

Overall survival in lower IPSS risk MDS by receipt of iron chelation therapy, adjusting for patient-related factors and measuring from time of first red blood cell transfusion dependence: an MDS-CAN analysis.

Analyses suggest iron overload in red blood cell (RBC) transfusion-dependent (TD) patients with myleodysplastic syndrome (MDS) portends inferior overall survival (OS) that is attenuated by iron chelation therapy (ICT) but may be biassed by unbalanced patient-related factors. The Canadian MDS Registry prospectively measures frailty, comorbidity and disability. We analysed OS by receipt of ICT, adjusting for these patient-related factors. TD International Prognostic Scoring System (IPSS) low and intermediate-1 risk MDS, at RBC TD, were included. Predictive factors for OS were determined. A matched pair analysis considering age, revised IPSS, TD severity, time from MDS diagnosis to TD, and receipt of disease-modifying agents was conducted. Of 239 patients, 83 received ICT; frailty, comorbidity and disability did not differ from non-ICT patients. Median OS from TD was superior in ICT patients (5·2 vs. 2·1 years; P < 0·0001). By multivariate analysis, not receiving ICT independently predicted inferior OS, (hazard ratio for death 2·0, P = 0·03). In matched pair analysis, OS remained superior for ICT patients (P = 0·02). In this prospective, non-randomized analysis, receiving ICT was associated with superior OS in lower IPSS risk MDS, adjusting for age, frailty, comorbidity, disability, revised IPSS, TD severity, time to TD and receiving disease-modifying agents. This provides additional evidence that ICT may confer clinical benefit.