Measurable residual disease assessment in apheresis product from multiple myeloma patients: Correlation with biology, depth of response and survival

While measurable residual disease (MRD) in bone marrow (bmMRD) is a validated surrogate biomarker in multiple myeloma (MM), the clinical relevance of MRD in the apheresis product (aMRD) remains unclear. We retrospectively analysed 422 MM patients who underwent autologous stem cell transplantation (ASCT) between 2005 and 2023 at the University Hospital of Salamanca, all evaluated for aMRD by 8-colour flow cytometry. Overall, 45 patients (10%) were aMRD+ve and 377 (90%) were aMRD-ve, with similar baseline characteristics except for a higher frequency of t(11;14) in aMRD+ve cases. Patients with responses worse than a very good partial response before apheresis were six times more likely to be aMRD+ve (odds ratio [OR] 6.6, p = 0.006), and notably, no patients with bmMRD-ve status prior to apheresis were aMRD+ve. After ASCT, patients with aMRD+ve exhibited lower rates of complete response and bmMRD-ve than patients with aMRD-ve, leading to a shorter progression-free survival (hazard ratio 1.7, p = 0.006), and aMRD+ve status was identified as an independent predictor of early relapse (OR 9.75, p = 0.007). These findings may suggest that aMRD+ve serves as a critical early biomarker to identify suboptimal treatment responses, reflecting bmMRD persistence and predicting inferior clinical outcomes.