Background:Hypomethylating agents (HMAs) have changed the treatment landscape for patients with higher-risk myelodysplastic syndromes (HR-MDS) in the past two decades. However, less than half of patients respond to HMA therapy and even the best responses are transient and non-curative. Therapeutic options for those who have failed HMAs are limited, and these patients have very poor prognosis. To speed the development of novel therapeutics, varying response rate definitions and event-free survival (EFS) have been suggested as clinical benefit endpoints for regulatory approvals. However, the relationship between complete remission (CR), partial remission (PR), hematologic improvement (HI), event-free survival (EFS) and overall survival (OS) in MDS has not been conclusively established. To evaluate the relationship between these endpoints, we conducted patient-level response analyses of MDS trials submitted to the FDA.