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

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Abstract

Measurable residual disease (MRD) in bone marrow (bmMRD) is an established surrogate biomarker in multiple myeloma (MM), but the clinical relevance of MRD in the apheresis product (aMRD) remains unclear. We retrospectively analyzed 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-color flow cytometry. Forty-five patients (10%) were aMRD + ve and 377 (90%) were aMRD-ve, and baseline characteristics were similar except for a higher frequency of t(11;14) in aMRD + ve cases. Most patients received ASCT as first-line therapy after induction based on proteasome inhibitors, immunomodulators with/without anti-CD38 monoclonal antibodies combinations. Of note, decting aMRD + ve was up to six times more likely in patients who had a response worse than very good partial response before apheresis (odds ratio (OR) 6.09, P  < 0.001). No patients in bmMRD-ve prior to apheresis were aMRD + ve. After ASCT, the aMRD + ve group exhibited lower rates of complete response and bmMRD-ve than patients with aMRD-ve, leading to a shorter progression-free survival (PFS) (hazard ratio 1.70, P  = 0.006), and aMRD + ve status was identified as an independent predictor of early relapse (OR 9.75, P  = 0.007). In conclusion, aMRD + ve may serve as a peripheral blood early biomarker to identify those with suboptimal responses, reflecting bmMRD persistence and predicting inferior PFS.

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