Predictors of unsustained measurable residual disease negativity in transplant-eligible multiple myeloma patients

Abstract

The role of measurable residual disease (MRD) negativity as a biomarker to stop treatment is being investigated in transplant-eligible multiple myeloma (MM). Thus, it is important to identify risk factors of MRD resurgence and/or progressive disease (PD) among patients achieving undetectable MRD in order to avoid undertreating them. Here, we studied 267 newly-diagnosed transplant-eligible MM patients enrolled in the GEM2012MENOS65 and GEM2014MAIN clinical trials who achieved MRD negativity by next-generation flow cytometry. After a median follow-up of 73 months since the first MRD negative assessment, 111 of the 267 (42%) patients showed MRD resurgence and/or PD. The only prognostic factors at diagnosis that predicted MRD resurgence and/or PD were an International staging system (ISS) 3 and the presence of ≥0.01% circulating tumor cells (CTCs). Failure to achieve MRD negativity after induction also predicted higher risk of MRD resurgence and/or PD. Patients having none versus one versus two or more risk factors (ISS 3, ≥0.01% CTCs and late MRD negativity) showed 5-year rates of MRD resurgence and/or PD of 16%, 33% and 57%, respectively (P<.001). Thus, these easily measurable risk factors could help refining the selection of patients for whom treatment cessation after MRD negativity is being investigated in clinical trials. Registered at www.clinicaltrials.gov with respective identifiers NCT01916252 and NCT02406144.