Blood-Based Measurable Residual Disease by Clonotypic Mass Spectrometry is Prognostic in Patients With Multiple Myeloma Undergoing Autologous Hematopoietic Cell Transplant

Background: While marrow-based measurable residual disease (MRD) testing for multiple myeloma (MM) is highly associated with outcomes, it is challenging to implement for serial monitoring. Consequently, blood-based MRD testing is desirable. Patients and Methods: In this study, we investigated the use of clonotypic mass spectrometry (CT-MS) for blood-based monitoring of M-protein in patients undergoing autologous hematopoietic cell transplant (AHCT). We performed a pilot analysis to assess assay performance, then restricted our analysis of CT-MS as a blood-based MRD assay to patients with 1) banked baseline samples pre-AHCT, 2) no M-protein on serum protein electrophoresis at day +100 post-AHCT and 3) available samples at day +100. Results: One hundred and eleven patients with analyzed, with 94 patients included in the MRD analysis. We derived a proposed threshold for MRD via the minimal P-value approach using two different methods. We found that CT-MS MRD-positivity at day + 100 post-AHCT was significantly associated with worse progression-free survival (PFS) (P < .0001, median PFS 2.5 vs. 8.4 years), with a HR of 3.74 (P = .0002). This association was stable on multi-variable analysis (MVA) adjusting for known risk factors (aHR: 3.68, P = .003). CT-MS MRD-positivity was also associated with significantly worse overall survival (median: 4.95 years vs. not reached, P = .001, HR: 3.95), stable on MVA (aHR: 3.25, P = .01). Conclusion: Our study suggests CT-MS may be a useful tool for blood-based MRD in multiple myeloma (MM).