What is the optimal time to initiate hypomethylating agents (HMAs) in higher risk myelodysplastic syndromes (MDSs)?

Hypomethylating agents (HMAs) are the standard of care for higher risk MDS (HR-MDS) patients. The current dogma is to begin HMA therapy in all HR-MDS patients at the time of initial diagnosis. We investigated the impact of the timing of HMA initiation among HR-MDS patients presenting with adequate blood counts to discern the possible benefit of early treatment based solely on disease risk. We identified 320 HR-MDS patients with adequate hematopoiesis who were treated with HMA. The complete response rates were 21%, 26%, 23%, and 7% respectively for patients treated within 30, 31-60, 61-90, and more than 90 days from time of diagnosis (p=.046). The median OS from the date of diagnosis was 641, 550, 979, and 806 days, respectively (p=.2). A delay in initiating HMA therapy in HR-MDS patients with adequate blood counts is not associated with worsened outcomes.