Predictors of Unsustained Minimal Residual Disease Negativity in Multiple Myeloma (MM) Patients

Abstract

The prognostic impact of achieving and in particular maintaining MRD negativity in multiple myeloma is now established, therefore identifying among MRD-negative patients the ones at higher risk of losing MRD negativity is of importance. We analyzed predictors of unsustained MRD-negativity in patients enrolled in the FORTE trial (NCT02203643). MRD was performed by multiparameter flow-cytometry (sensitivity of 10-5) at premaintenance and every 6 months thereafter. The cumulative incidence (CI) of MRD resurgence and/or progression was analyzed in MRD-negative patients. 306/474 (65%) MRD-negative patients were analyzed. After a median follow-up of 50.4 months from MRD-negativity, 185/306 (60%) patients were still MRD-negative and progression-free, 118 (39%) lost their MRD-negative status and 3 patients (1%) died without progression. Amp1q vs. normal (4-years CI 63% vs 34), ≥2 concomitant high-risk cytogenetic abnormalities vs. 0 (4-years CI 59% vs 33%), Circulating tumor cells at baseline (high vs. low 4-years CI 62% vs. 32%) and time-to-reach MRD negativity post-consolidation vs. pre-consolidation (4-years CI 46% vs 35%) were associated with a higher risk of unsustained MRD-negativity in a multivariate Fine-Grey model. During the first 2 years of maintenance, patients receiving carfilzomib-lenalidomide vs. lenalidomide alone had a lower risk of unsustained MRD-negativity (4-years CI 20% vs 33%). CT# NCT02203643