@article{2999635,
    title = "Sustained minimal residual disease negativity in newly diagnosed multiple myeloma and the impact of daratumumab in MAIA and ALCYONE",
    author = "San-Miguel, J. and Avet-Loiseau, H. and Paiva, B. and Kumar, S. and Dimopoulos, M.A. and Facon, T. and Mateos, M.-V. and Touzeau, C. and Jakubowiak, A. and Usmani, S.Z. and Cook, G. and Cavo, M. and Quach, H. and Ukropec, J. and Ramaswami, P. and Pei, H. and Qi, M. and Sun, S. and Wang, J. and Krevvata, M. and DeAngelis, N. and Heuck, C. and Van Rampelbergh, R. and Kudva, A. and Kobos, R. and Qi, M. and Bahlis, N.J.",
    journal = "Blood advances",
    year = "2022",
    volume = "139",
    number = "4",
    pages = "492-501",
    publisher = "Elsevier B.V.",
    doi = "10.1182/blood.2020010439",
    keywords = "bortezomib;  daratumumab;  dexamethasone;  lenalidomide;  melphalan;  prednisone;  antineoplastic agent;  daratumumab;  monoclonal antibody, aged;  Article;  cancer control;  cancer patient;  cancer prognosis;  cancer regression;  cancer risk;  cancer staging;  cancer survival;  clinical feature;  clinical outcome;  controlled study;  demographics;  disease exacerbation;  drug efficacy;  follow up;  high throughput sequencing;  human;  intention to treat analysis;  kidney function;  major clinical study;  minimal residual disease;  mortality risk;  multicenter study;  multiple cycle treatment;  multiple myeloma;  open study;  overall survival;  phase 3 clinical trial;  progression free survival;  randomized controlled trial;  risk assessment;  time to treatment;  treatment response;  clinical trial;  female;  male;  middle aged;  minimal residual disease;  multiple myeloma;  treatment outcome, Aged;  Antibodies, Monoclonal;  Antineoplastic Combined Chemotherapy Protocols;  Female;  Humans;  Male;  Middle Aged;  Multiple Myeloma;  Neoplasm, Residual;  Progression-Free Survival;  Treatment Outcome",
    abstract = "In patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM), daratumumab reduced the risk of disease progression or death by 44% in MAIA (daratumumab/lenalidomide/dexamethasone [D-Rd]) and 58% in ALCYONE (daratumumab/bortezomib/melphalan/prednisone [D-VMP]). Minimal residual disease (MRD) is a sensitive measure of disease and response to therapy. MRD-negativity status and durability were assessed in MAIA and ALCYONE. MRD assessments using next-generation sequencing (10−5) occurred for patients achieving complete response (CR) or better and after at least CR at 12, 18, 24, and 30 months from the first dose. Progression-free survival (PFS) by MRD status and sustained MRD negativity lasting ≥6 and ≥12 months were analyzed in the intent-to-treat population and among patients achieving at least CR. In MAIA (D-Rd, n = 368; lenalidomide and dexamethasone [Rd], n = 369) and ALCYONE (D-VMP, n = 350; bortezomib/melphalan/prednisone [VMP], n = 356), the median duration of follow-up was 36.4 and 40.1 months, respectively. MRD-negative status and sustained MRD negativity lasting ≥6 and ≥12 months were associated with improved PFS, regardless of treatment group. However, daratumumab-based therapy improved rates of MRD negativity lasting ≥6 months (D-Rd, 14.9% vs Rd, 4.3%; D-VMP, 15.7% vs VMP, 4.5%) and ≥12 months (D-Rd, 10.9% vs Rd, 2.4%; D-VMP, 14.0% vs VMP, 2.8%), both of which translated to improved PFS vs control groups. In a pooled analysis, patients who were MRD negative had improved PFS vs patients who were MRD positive. Patients with NDMM who achieved MRD-negative status or sustained MRD negativity had deep remission and improved clinical outcomes. These trials were registered at www.clinicaltrials.gov as #NCT02252172 (MAIA) and #NCT02195479 (ALCYONE). © 2022 American Society of Hematology"
}