Key clinical point: Baseline and serial molecular profiling by next-generation sequencing (NGS) can predict outcomes with hypomethylating agents (HMAs) in myelodysplastic syndromes (MDS). Serial molecular profiling during therapy of patients with mutant TP53 can identify patients who may benefit from allogeneic transplantation.
Major finding: Mutations in TET2 and ASXL1 genes emerged as the most informative variables associated with response to HMA therapy (overall response rate, 62.1%; complete remission rate, 34.5%). The number of mutations detected by NGS (hazard ratio [HR], 1.22; P = .02) and mutations in TP53 (HR, 2.33; P = .001) and EZH2 (HR, 2.41; P = .04) were independent covariates associated with inferior overall survival (OS). Serial molecular profiling demonstrated that clearance of TP53 mutations during HMA therapy was associated with superior OS (HR, 0.28; P = .001) and improved outcome in patients proceeding to allogeneic transplantation.
Study details: This study evaluated response and OS in 247 patients molecularly profiled by NGS before first-line HMA therapy; a subset of 108 patients were sequenced serially during treatment.
Disclosures: This study was supported in part by the S Foundation Young Investigator Grant, the Early Career Award of the Dresner Foundation, and the Edward P. Evans Foundation Award. DA Sallman, E Padron, and AF List received research funding from Celgene. The remaining authors declared no conflicts of interest.
Source: Hunter AM et al. Blood Adv. 2021 Feb 23. doi: 10.1182/bloodadvances.2020003508 .