Dp118 | Real-world Analysis of Minimal Residual Disease in Transplant-eligible Newly Diagnosed Multiple Myeloma Patients: a Decade of Single-center Experience
Year: 2025
Type: article
Abstract: BACKGROUND: Minimal Residual Disease (MRD) in multiple myeloma (MM) is a recognized surrogate marker for progression-free survival (PFS) and a potential clinical trial endpoint. MRD negativity is associated with improved survival, regardless of disease setting, assessment method, cytogenetic risk, or assay sensitivity. METHODS: We conducted a single-center, retrospective real-life analysis of 185 newly diagnosed MM patients eligible for ASCT, treated at AOU Careggi from Feb 2013 to Dec 2023. Patients received VTD induction until Dec 2021, then Dara-VTD per CASSIOPEIA protocol. Lenalidomide maintenance was introduced from Nov 2018. MRD was assessed on bone marrow samples using 2nd-generation 8-color flow cytometry (sensitivity 10⁻⁵) at two key time points: post-induction and post-ASCT/pre-maintenance. RESULTS: Median age was 58 (range 32–69), M/F: 97/88. High-risk (HiR) cytogenetic abnormalities [del(17p), t(4;14), t(14;16), gain/amp(1q)] were present in 33% (n=61). 141 patients (76%) received VTD induction regimen, whereas 44 (24%) were treated with Dara-VTD. Most patients (80%) underwent single ASCT; 20% received tandem ASCT due to HiR status. Lenalidomide maintenance was administered to 59% (n=109). Post-induction, the overall response rate was 99.4%, with ≥VGPR in 82% and ≥CR in 27%. MRD negativity was achieved in 40.5% (n=75), increasing from 37% (VTD) to 52% (Dara-VTD). Pre-maintenance, 55% reached ≥CR, and MRD- was observed in 70.8% overall (67% VTD vs 81% Dara-VTD). After a median follow-up of 63 months, median PFS (mPFS) was 71 months. MRD- status correlated with improved mPFS both post-induction (92.3 vs 56.6 months, p=0.01) and pre-maintenance (98 vs 46 months, p<0.001). Among patients with ≥VGPR, MRD negativity was associated with longer PFS (88 vs 52 months, p=0.01). In HiR patients, MRD negativity conferred a PFS benefit, aligning their outcomes with standard-risk patients (85 vs 35 months for HiR MRD+, p<0.001). Bone marrow re-assessment ≥12 months from the prior was available in 52 patients on maintenance therapy. Among these, 44 showed a sustained MRD-, while 8 converted to MRD+. Median PFS was significantly shorter in those who lost MRD- (NR in MRD- vs 44 in MRD loss vs 43 months in patients with persistent MRD+, p<0.001). CONCLUSIONS: Our real-world study confirms MRD as a strong early predictor of PFS, underscores the prognostic value of sustained MRD negativity, and highlights its favorable impact, particularly in high-risk patients.
Authors: I. Attucci, C. Nozzoli, R. Boncompagni, B. Peruzzi, R. Caporale, L. Pengue, M. Messeri, A. M. Vannucchi, E. Antonioli
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7093122532
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