Blood-Based Mass Spectrometry MRD Rivals Bone Marrow NGS in Multiple Myeloma
Targeted mass spectrometry for minimal residual disease detection in serum was compared with next-generation sequencing on bone marrow in 41 myeloma patients from the IFM-2009 trial. MS-MRD proved significantly more sensitive than standard electrophoretic methods, showed 79% concordance with NGS-MRD, and patients negative by both methods had the longest progression-free survival at 96 months. The study provides proof-of-principle that blood-based MS-MRD could offer a patient-friendly alternative to invasive bone marrow assessment.
The original study
Multiple Myeloma Minimal Residual Disease Detection: Targeted Mass Spectrometry in Blood vs Next-Generation Sequencing in Bone Marrow.
- Authors
- Langerhorst P, Noori S, Zajec M, De Rijke YB, Gloerich J, van Gool AJ, et al.
- Journal
- Clinical chemistry
- Type
- Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't
- PMID
- 34643690
Original abstract
BACKGROUND: Minimal residual disease (MRD) status assessed on bone marrow aspirates is a major prognostic biomarker in multiple myeloma (MM). In this study we evaluated blood-based targeted mass spectrometry (MS-MRD) as a sensitive, minimally invasive alternative to measure MM disease activity. METHODS: Therapy response of 41 MM patients in the IFM-2009 clinical trial (NCT01191060) was assessed with MS-MRD on frozen sera and compared to routine state-of-the-art monoclonal protein (M-protein) diagnostics and next-generation sequencing (NGS-MRD) at 2 time points. RESULTS: In all 41 patients we were able to identify clonotypic M-protein-specific peptides and perform serum-based MS-MRD measurements. MS-MRD is significantly more sensitive to detect M-protein compared to either electrophoretic M-protein diagnostics or serum free light chain analysis. The concordance between NGS-MRD and MS-MRD status in 81 paired bone marrow/sera samples was 79%. The 50% progression-free survival (PFS) was identical (49 months) for patients who were either NGS-positive or MS-positive directly after maintenance treatment. The 50% PFS was 69 and 89 months for NGS-negative and MS-negative patients, respectively. The longest 50% PFS (96 months) was observed in patients who were MRD-negative for both methods. MS-MRD relapse during maintenance treatment was significantly correlated to poor PFS (P < 0.0001). CONCLUSIONS: Our data indicate proof-of-principle that MS-MRD evaluation in blood is a feasible, patient friendly alternative to NGS-MRD assessed on bone marrow. Clinical validation of the prognostic value of MS-MRD and its complementary value in MRD-evaluation of patients with MM is warranted in an independent larger cohort.