Peripheral Blood Mass Spectrometry Provides Non-Invasive MRD Assessment in Post-Transplant Myeloma
Using EXENT mass spectrometry on serum samples from 138 patients in the phase 3 ATLAS trial, investigators demonstrated feasibility of blood-based MRD detection in post-transplant myeloma without pretreatment calibration. Sustained MS negativity in peripheral blood carried similar prognostic performance to bone marrow MRD negativity at 10-5 sensitivity, and combined blood/marrow MRD negativity identified patients with superior PFS, pointing toward less invasive MRD monitoring strategies.
The original study
Mass spectrometry-based assessment of M protein in peripheral blood during maintenance therapy in multiple myeloma.
- Authors
- Kubicki T, Dytfeld D, Barnidge D, Sakrikar D, Przybyłowicz-Chalecka A, Jamroziak K, et al.
- Journal
- Blood
- Type
- Clinical Trial, Phase III, Journal Article, Research Support, Non-U.S. Gov't
- PMID
- 38713888
Original abstract
Mass spectrometry (MS) can detect multiple myeloma-derived monoclonal proteins in the peripheral blood (PB) with high sensitivity, potentially serving as a PB assay for measurable residual disease (MRD). This study evaluated the significance of PB MS MRD negativity during posttransplant therapy in patients with newly diagnosed multiple myeloma. Serum samples from 138 patients treated in the phase 3 ATLAS trial of posttransplant maintenance with either carfilzomib, lenalidomide, and dexamethasone, or with lenalidomide alone were analyzed using EXENT MS methodology. We established feasibility of measuring MRD by MS in the PB in the posttransplant setting, despite unavailability of pretreatment calibration samples. There was high agreement between MRD by MS in the PB and paired bone marrow (BM) MRD results at the 10-5 threshold, assessed by either next-generation sequencing (NGS) or multiparameter flow cytometry (MFC) (70% and 67%, respectively). Agreement between PB MS and both BM MRD methods was lowest early after transplant and increased with time. MS negativity was associated with improved progression-free survival (PFS), which, in landmark analysis, reached statistical significance after 18 cycles after transplant. Combined PB/BM MRD negativity by MFC or NGS was associated with superior PFS compared with MRD negativity by only 1 modality. Sustained MS negativity carried similar prognostic performance to sustained BM MRD negativity at the 10-5 threshold. Overall, posttransplant MS assessment was feasible and provided additional prognostic information to BM MRD negativity. Further studies are needed to confirm the role and optimal timing of MS in disease evaluation algorithms. The ATLAS trial is registered at www.clinicaltrials.gov as #NCT02659293.