Minimal residual disease measurement in blood by mass spectrometry identifies long-term responders in multiple myeloma.

Modern multiple myeloma treatment enables deep and sustained responses, necessitating assessment of minimal residual disease (MRD) in the bone marrow to refine response categorization. Recently, mass spectrometry (MS)-based methods have emerged as highly sensitive tools for measuring MRD in the peripheral blood. However, the role specific MS techniques play in response categorization has yet to be established. We pooled data from 97 patients treated in 3 prospective phase 2 trials evaluating carfilzomib-based triplets and quadruplets, with or without autologous stem cell transplantation. MRD was assessed in the bone marrow using next-generation sequencing (NGS) and in the peripheral blood with 2 MS methods: matrix-assisted laser desorption ionization-time of flight (EXENT) and the more sensitive liquid chromatography-MS (LC-MS). EXENT negativity was associated with superior progression-free survival (PFS) and overall survival. LC-MS negativity identified patients with long-term responses. EXENT complemented NGS MRD, with patients with double negativity experiencing longer PFS than those negative in only 1 modality. Patients negative by both LC-MS and NGS MRD at 10 had a 5-year PFS rate of 89%. These findings support incorporating MS into MRD response assessment and in prognostic algorithms in myeloma. In addition, our results indicate that LC-MS can provide valuable end point in future studies aiming for functional cure.