Minimal residual disease (MRD) is one of the most important prognostic factors in multiple myeloma (MM) and a valid surrogate for progression-free survival (PFS) and overall survival (OS). Recently, MRD negativity was approved as an early clinical endpoint for accelerated drug approval in MM. Nevertheless, there is limited evidence of MRD utility in real-world setting. In this retrospective multicenter study, we report outcomes of 331 newly diagnosed MM patients with MRD evaluation at Day+100 after autologous stem cell transplantation using flow cytometry with a median limit of detection of 0.001%. MRD negativity was reached in 47% of patients and was associated with significantly prolonged median PFS (49.2 months vs. 18.4 months; hazard ratios (HR) = 0.37; p < 0.001) and OS (not reached vs. 74.9 months; HR = 0.50; p = 0.007). Achieving MRD negativity was associated with PFS improvements regardless of age, International Staging System (ISS) stage, lactate dedydrogenase (LDH) level, or cytogenetic risk. Importantly, MRD positive patients benefited from lenalidomide maintenance versus no maintenance (18-months PFS: 81% vs. 46%; HR = 0.24; p = 0.002) while in MRD negative patients such benefit was not observed (p = 0.747). The outcomes of our real-world study recapitulate results from clinical trials including meta-analyses and support the idea that MRD positive patients profit more from lenalidomide maintenance than MRD negative ones.

1st Medical Department Clinical Department of Haematology of the 1st Faculty of Medicine and General Teaching Hospital Charles University Prague Czech Republic

4th Department of Internal Medicine Hematology University Hospital Hradec Kralove Charles University Faculty of Medicine in Hradec Kralove Hradec Kralove Czech Republic

Department of Biology and Ecology Faculty of Science University of Ostrava Ostrava Czech Republic

Department of Clinical Hematology University Hospital Brno Brno Czech Republic

Department of Hemato Oncology University Hospital Olomouc and Faculty of Medicine and Dentistry Palacky University Olomouc Czech Republic

Department of Hematooncology Faculty of Medicine University of Ostrava Ostrava Czech Republic

Department of Hematooncology University Hospital Ostrava Ostrava Czech Republic

Department of Internal Medicine Hematology and Oncology University Hospital Brno and Faculty of Medicine Masaryk University Brno Czech Republic

Hematology and Oncology Department Charles University Hospital Pilsen Pilsen Czech Republic

Institute of Clinical Immunology and Allergology Faculty of Medicine University Hospital and Charles University Hradec Kralove Czech Republic

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