Serum MALDI-TOF Mass Spectrometry Tracks Bone Marrow MRD Through Maintenance in 237 CASSIOPEIA Myeloma Patients, Blood Reports

Paired samples from a structured trial schedule

CASSIOPEIA randomized transplant-eligible newly diagnosed myeloma patients to bortezomib, thalidomide and dexamethasone with or without daratumumab, then re-randomized those still on study to daratumumab maintenance or observation. Its 2025 long-term MRD paper in Blood, with Jill Corre of the Toulouse Oncopole as first author, reported 10^-5 MRD-negativity after consolidation of 63.7% with daratumumab versus 43.7% without, at a median follow-up of 80.1 months. The new analysis takes advantage of that fixed sampling calendar. Dejoie and colleagues, a group spanning Nantes, Toulouse, Bordeaux, Poitiers, Paris and Lyon, used serum and marrow drawn at the same protocol visits in 237 patients enrolled in CASSIOPET, and compared mass spectrometry against NGF and NGS for association with PFS, agreement between methods, longitudinal change and sustained MRD status under International Myeloma Working Group criteria.

The serum method measures the patient's own monoclonal immunoglobulin by MALDI-TOF. The authors' IMS 2025 poster on an earlier cut of the same cohort specified the platform as the EXENT Analyser from The Binding Site, part of Thermo Fisher Scientific, and the Blood abstract describes the approach as a non-invasive alternative to marrow sampling that is "invasive and subject to sampling variability."

Strong against 10^-5 marrow, "more limited" at 10^-6

The full paper sits behind the ASH paywall and has no PubMed Central copy, so the quantitative results below come from the abstract and from the September 2025 poster, which the authors presented ahead of publication and which may differ from the final figures. In the poster, paired samples were available at day 100 after transplant (n=162) and at weeks 25 (160), 52 (130) and 105 (112). At day 100, patients positive by mass spectrometry had a median PFS of 38.1 months (HR 0.42, 95% CI 0.27-0.64), compared with 42.1 months for NGF-positive (HR 0.58) and 42.9 months for NGS-positive patients at 10^-5 (HR 0.59). At week 52 the three hazard ratios tightened to 0.20, 0.17 and 0.15. Median PFS was not reached at any time point for patients negative by either blood or marrow. The poster gave a serum-MS negative predictive value of 0.90 at day 100 and 0.87 at week 52 against 10^-5 marrow, and positive predictive values of 0.83 and 0.90.

The Blood abstract adds two findings the poster did not carry. Agreement between serum MS and marrow MRD improved during the maintenance phase, and the blood test's rule-out performance against NGS at the deeper 10^-6 threshold was described as "more limited." Sustained MRD negativity over one and two years picked out patients with favorable outcomes irrespective of method.

Where the authors draw the line

"These findings support a complementary, phase-adapted role for serum MS alongside bone marrow MRD testing, enabling frequent non-invasive monitoring during maintenance while preserving bone marrow assessment when maximum sensitivity is required," the abstract states. The study is a retrospective post-hoc analysis, the time points run from post-induction through maintenance, and the comparison against 10^-6 NGS is where blood falls short. The abstract does not report how the serum assay handled daratumumab interference or light-chain-only disease, two questions a laboratory will want answered from the full text.

Why This Matters to the APO|APE Reader

The Corre paper's 10^-6 marrow rates, 60.7% versus 52.0% on daratumumab maintenance versus observation after D-VTd, show how much of the deep-response signal in CASSIOPEIA lives at the sensitivity where serum MS ruled out least well. A decision to substitute blood for a marrow at week 105 therefore trades the aspirate for a test with a documented 10^-6 gap, and the Blood paper is the first CASSIOPEIA data set to put that trade on a protocol timeline. The poster names a commercial platform, EXENT, rather than a research-only method, which puts the maintenance-phase workflow within reach of a clinical chemistry laboratory that already runs MALDI-TOF for M-protein work.