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    MRD and Biomarkers

    Category: MRD and Biomarkers

    Mass Spectrometry vs. 10-5 MRD Detection by Next-Generation Flow and Sequencing in Multiple Myeloma: Results from the Cassiopeia Clinical Trial

    (PA-169) Mass Spectrometry vs. 10-5 MRD Detection by Next-Generation Flow and Sequencing in Multiple Myeloma: Results from the Cassiopeia Clinical Trial

    Wednesday, September 17, 2025
    Introduction: The detection of minimal residual disease(MRD) is crucial for evaluating treatment response in Multiple Myeloma(MM). Achieving 10-5 MRD sensitivity is recommended by the IMWG for accurate disease remission assessment, correlating with better long-term outcomes and sustained remission. Recently, mass spectrometry(MS) has emerged as a promising tool for MRD detection, offering a significant clinical advantage by being less invasive as it can be performed on peripheral blood.

    Methods: Our goal is to compare the impact of MS versus MRD detected by NGF and NGS with a sensitivity level of 10-5 on patient outcomes post-treatment in a cohort from the Cassiopeia clinical trial, a Phase 3 study evaluating the addition of daratumumab to bortezomib, thalidomide, and dexamethasone(VTd) induction/consolidation and with daratumumab maintenance vs. observation in transplant-eligible newly diagnosed MM. This study examines MRD detection in paired samples(with NGF/NGS and MS available) at +100 days post-ASCT(n=162) and at weeks 25(n=160), 52(n=130), and 105(n=112), providing a longitudinal perspective on MRD's prognostic significance.  MS was assessed by MALDI-ToF with the EXENT® Analyser (The Binding Site, part of Thermo Fisher Scientific).

    Results:

    At +100 days, the MS+ group had a median progression-free survival(mPFS) of 38.1 months (mo)(HR 0.42, 95% CI:0.27-0.64,p< 0.0001). The NGF+10-5 group had a mPFS of 42.1 mo(HR 0.58, 95% CI:0.37-0.91,p=0.0124), and the NGS+10-5 group had a mPFS of 42.9 mo(HR 0.59, 95% CI:0.38-0.92,p=0.0164).

    At week 52, the MS+ group had a mPFS of 21.6 mo (HR 0.20, 95% CI:0.11-0.39,p< 0.0001). The NGF+10-5 group showed a mPFS of 19.8 mo(HR 0.17, 95% CI:0.09-0.33,p< 0.0001), and the NGS+10-5 group had a mPFS of 21.4 mon(HR 0.15, 95% CI:0.08-0.29,p< 0.0001).

    At other time points(week 25 and week 105), the MS+, NGF+10-5, and NGS+10-5 groups showed similar significant inferior mPFS.

    However, at all time points, mPFS was not yet reached for patients achieving MS- and 10-5 NGF-/NGS-.

    The MS negative predictive value(NPV) at +100 days and week 52, compared to 10-5 NGF and NGS, was 0.90(CI:0.82-0.94) and 0.87(CI:0.78-0.92), respectively. The MS positive predictive value(PPV) at +100 days and week 52, compared to 10-5 NGF and NGS, was 0.83(CI:0.67-0.91) and 0.90(CI:0.78-0.92), respectively.

    Conclusions: These findings highlight the prognostic significance of MRD using MS and NGF/NGS at a 10-5 sensitivity level across multiple time points in the Cassiopeia clinical trial. Not reaching mPFS for the MS- and 10-5MRD- groups underscores the potential for prolonged remission, indicating the high efficacy of these methods in predicting better long-term outcomes.