MINIMAL residual disease (MRD) assessment is a key prognostic marker in multiple myeloma (MM), offering insights into patient survival and disease progression. At the University of California, San Francisco (UCSF), a retrospective study analysed MRD status in 482 MM patients diagnosed from 2008–2020.
MRD assessment was conducted using next-generation sequencing (NGS) of immunoglobulin (Ig) genes, focusing on the long-term impact of response depth and clonal diversity on clinical outcomes. Progression-free survival (PFS) curves were plotted using the Kaplan-Meier method. Among newly diagnosed patients, 119 out of 304 achieved MRD negativity at a sensitivity level of 10-6, leading to significantly prolonged PFS compared to those with persistent MRD positivity (p > 0.0001). In the relapsed group, 64 of 178 patients reached MRD negativity at 10-6, similarly showing improved PFS compared to their MRD-positive counterparts (p=0.03).
MRD dynamics were classified into three categories: patients with consistently MRD-negative samples, those with declining but detectable clones, and patients with stable or increasing clone counts. The first two groups had significantly longer PFS than the third (p<10-7), highlighting the importance of MRD dynamics as a predictor of clinical outcomes.
In addition, clonal diversity, or the number of unique Ig sequences in each sample, was found to correlate with better PFS outcomes. Patients who were MRD-positive but had not relapsed exhibited higher clonal diversity than those who relapsed, suggesting that clonal diversity might indicate stronger immune recovery and prolonged disease control.
These findings emphasise that MRD dynamics and clonal diversity assessments can complement traditional MRD evaluation in predicting multiple myeloma outcomes. Together, these factors can help guide clinical decision-making, identifying patients at higher risk of relapse and allowing for earlier treatment interventions to improve long-term prognosis.
Katie Wright, EMJ
Reference
Martinez-Lopez J et al. Measurable residual disease (MRD) dynamics in multiple myeloma and the influence of clonal diversity analyzed by artificial intelligence. Blood Cancer J. 2024;14(1):131.
