ctDNA-NGS for peripheral blood MRD monitoring in NDMM

Results from a study investigating peripheral blood measurable residual disease (MRD) monitoring in 84 patients with newly diagnosed multiple myeloma (NDMM) enrolled in PETHEMA/GEM clinical trials were published in HemaSphere by Buenache et al. A total of 292 longitudinal peripheral blood samples were analyzed using a highly sensitive next-generation sequencing (NGS) assay targeting patient-specific somatic mutations in circulating tumor DNA (ctDNA), alongside bone marrow (BM)-MRD assessment using next-generation flow cytometry (NGF). 

Key data: The ctDNA-NGS assay demonstrated a higher positive predictive value (PPV; 88.9% vs 34.5%) and specificity (98.4% vs 70.3%) for predicting relapse than BM-MRD assessment by NGF, although sensitivity was lower (61.5% vs 83.3%). Detectable ctDNA was independently associated with an increased risk of progression and/or death in multivariable analysis (hazard ratio [HR], 11.5; 95% confidence interval [CI], 2.66–49.4; p < 0.001). The assay demonstrated 92% applicability across the study population. 

Key learning: High-sensitivity ctDNA detection by NGS in peripheral blood demonstrated high specificity for MRD monitoring and identified patients at increased risk of relapse, supporting further evaluation of ctDNA-based peripheral blood MRD assessment as a complementary approach to BM-MRD assessment.