Validation of the International Working Group 2023 response criteria for higher risk myelodysplastic syndromes/neoplasms using the International Consortium for Myelodysplastic Syndromes VALIDATE database and a randomized phase III trial

Response assessment criteria in patients with higher-risk myelodysplastic syndromes/neoplasms (HR-MDS) have been updated in the 2023 International Working Group (IWG) criteria. However, validation of these criteria has been limited to date. We analyzed overall survival (OS) by best response according to IWG 2023 criteria in two separate and independent cohorts of patients with HR-MDS who were treated with hypomethylating agents (HMA)-based therapies. The first dataset was the International Consortium for MDS (icMDS) VALIDATE retrospective database, and the second dataset was the cohort of HR-MDS patients treated in the randomized, phase III PANTHER trial of azacitidine + pevonedistat or placebo. A total of 1,268 patients (VALIDATE: n=1,047; PANTHER: n=221) were evaluated in two separate sets of analyses according to the source dataset. Patients who achieved composite CR (cCR) had improved OS compared to patients not achieving cCR in both datasets and in both univariate and multivariable analyses (VALIDATE: multivariable Hazard Ratio [HR]: 0.65; 95% CI: 0.55-0.76; p.