MDS-261 Systematic Literature Review (SLR) to Identify the Burden of Illness and Treatment Effectiveness in ESA-Refractory or Relapsed, Transfusion-Dependent, Low-Risk MDS

Abstract

Myelodysplastic syndromes (MDS) are orphan, rare diseases with an incidence rate of 4.6 (US) per 100,000; 75% are low-risk MDS (LR-MDS). Approximately 50% of LR-MDS patients develop transfusion-dependent (TD) anemia irrespective of ring sideroblasts (RS) status. There are no approved treatments for RS-LR-MDS. To identify the burden of illness, treatment patterns, and costs for ESA-refractory or relapsed (ESA-r/r) LR-MDS by conducting real-world evidence (RWE), economic, and HRQoL systematic literature reviews (SLRs). SLRs conducted following PRISMA guidelines, supplemented with conference proceedings (ASCO, EHA, ISPOR, ESMO, ASH). ESA-r/r, TD, LR-MDS patients. ESAs, HMAs, lenalidomide, luspatercept, imetelstat, rigosertib. Overall survival (OS), hematological improvement (HI), transfusion independence (TI), HRQoL, costs, hospitalization. 9/28 RWE studies included ESA-r/r populations; two studies reported lower OS compared with responding patients. 6/28 RWE studies contained a TD population; in three, HI was worse in TD patients compared to TI populations. No RWE studies reported an RS+, TD population; however, while RS status did not impact TI, OS was significantly longer in RS+ populations (2.8 vs. 2.1 years, p<0.01; US SEER Medicare-linked database). 5/14 HRQoL studies found TD LR-MDS subjects had lower HRQoL than TI subjects (EQ-5D, FACT-An, EORTC-QLQ-C30). Evidence from the MDS-CAN registry suggested that transfusion burden negatively affects HRQoL in RS+ LR-MDS. In the MEDALIST trial, ESA-r/r, RS+, LR-MDS patients had a higher disease burden (physical functioning, role functioning, social functioning, fatigue, dyspnea) relative to the general population. RS+, TD populations are associated with 3-fold higher costs compared to TI populations, increased risk of hospitalization (OR 1.3 95% CI 1.15 - 1.46), and lower HRQoL in France and Canada. Transfusion-related costs were the largest contributor to the economic burden of LR-MDS in these two studies (US, 2008-2013; France, 2012-2013). While TI is not well-defined or commonly reported in RWE, ESA-r/r, TD LR-MDS populations (RS+/-) have worse outcomes with RS- status significantly reducing survival. The continued use of ESAs and HMAs in ESA-r/r LR-MDS demonstrates a high unmet need. New therapies that reduce transfusions and improve durability across RS status may improve HRQoL and outcomes. Nishan Sengupta, Geron Corporation.