Clinical Impact of Panel Based Error Corrected Next Generation Sequencing versus Flow Cytometry to Detect Measurable Residual Disease (MRD) in Acute Myeloid Leukemia (AML)

We accrued 201 patients of adult AML treated with conventional therapy, in morphological remission and evaluated MRD using sensitive error corrected next generation sequencing (NGS-MRD) and multiparameter flow cytometry (FCM-MRD) at the end of induction (PI) and consolidation (PC). Nearly 71% of patients harbored PI NGS-MRD and 40.9% harbored PC NGS-MRD (median VAF 0.76%). Patients harboring NGS-MRD had a significantly higher cumulative incidence of relapse (p=0.003), inferior overall survival (p=0.001) and relapse free survival (p<0.001) as compared to NGS-MRD negative patients. NGS-MRD was predictive of inferior outcome in intermediate cytogenetic risk and demonstrated potential in favorable cytogenetic risk AML. Patients who cleared PI NGS-MRD had a significantly improved survival as compared to patients who became negative subsequently indicating that kinetics of NGS-MRD clearance was of paramount importance. NGS-MRD identified over 80% of cases identified by flow cytometry at PI time point whereas FCM identified 49.3% identified by NGS. Only a fraction of cases were truly missed by NGS as compared to FCM-MRD. NGS-MRD emerged as the most important independent prognostic factor predictive of inferior outcome (p<0.001). We demonstrate a widely applicable, scalable NGS-MRD approach that is clinically informative and advantageous when compared to FCM-MRD in AML treated with conventional therapies.