Manuela Gambella, Barbara Gamberi, Pieter Sonneveld, Elona Saraci, Massimo Offidani, Antonio Palumbo, Alberto Rocci, Annalisa Bernardini, Vittorio Emanuele Muccio, Sara Grammatico, Mario Boccadoro, Stefano Spada, Paola Omedè, Rossella Troia, Concetta Conticello, Michele Cavo, Alessandra Larocca, Milena Gilestro, Anna Marina Liberati, Stefania Oliva, Gambella, Manuela, Omedé, Paola, Spada, Stefano, Muccio, Vittorio Emanuele, Gilestro, Milena, Saraci, Elona, Grammatico, Sara, Larocca, Alessandra, Conticello, Concetta, Bernardini, Annalisa, Gamberi, Barbara, Troia, Rossella, Liberati, Anna Marina, Offidani, Massimo, Rocci, Alberto, Palumbo, Antonio, Cavo, Michele, Sonneveld, Pieter, Boccadoro, Mario, Oliva, Stefania, and Hematology
Background: Minimal residual disease (MRD) is one of the most relevant prognostic factors in patients with multiple myeloma (MM); however, the impact of maintenance therapy on MRD levels remains unclear. Among patients with newly diagnosed MM (NDMM) who received lenalidomide maintenance until they developed disease progression, the role of MRD status as a predictor of progression-free survival (PFS) was evaluated by multiparameter flow cytometry (MFC) and allelic-specific oligonucleotide real-time quantitative polymerase chain reaction (ASO-RQ-PCR) analysis. Methods: Seventy-three patients with NDMM enrolled in the RV-MM-EMN-441 (clinical trials.gov identifier, NCT01091831) and RV-MM-COOP-0556 (clinicaltrials.gov identifier, NCT01208766; European Myeloma Network EMN02/HO95 MM Trial) phase 3 trials who achieved at least a very good partial response after intensification/consolidation were included. The median patient age was 57 years (interquartile range, 53-61 years), and all patients received lenalidomide maintenance until they developed progression. MRD was evaluated on bone marrow after intensification/consolidation, after 6 courses of maintenance, and every 6 months thereafter until clinical relapse using both ASO-RQ-PCR (sensitivity, 10 −5 ) and MFC (sensitivity, from 10 −4 to 10 −5 ). Results: After intensification/consolidation, 33 of 72 patients (46%) achieved a molecular complete response (m-CR), and 44 of 70 (63%) achieved a flow complete response (flow-CR). Almost 27% of patients who were MRD-positive after consolidation became MRD-negative during maintenance. After a median follow-up of 38 months, PFS was prolonged in patients who achieved negative MRD status during maintenance according to results from both ASO-RQ-PCR analysis (hazard ratio, 0.29; 95% confidence interval, 0.14-0.62; P =.0013) and MFC (hazard ratio, 0.19; 95% confidence interval, 0.09-0.41; P