TY - JOUR
TI - Sustained minimal residual disease negativity in newly diagnosed multiple myeloma and the impact of daratumumab in MAIA and ALCYONE
AU - San-Miguel, J.
AU - Avet-Loiseau, H.
AU - Paiva, B.
AU - Kumar, S.
AU - Dimopoulos, M.A.
AU - Facon, T.
AU - Mateos, M.-V.
AU - Touzeau, C.
AU - Jakubowiak, A.
AU - Usmani, S.Z.
AU - Cook, G.
AU - Cavo, M.
AU - Quach, H.
AU - Ukropec, J.
AU - Ramaswami, P.
AU - Pei, H.
AU - Qi, M.
AU - Sun, S.
AU - Wang, J.
AU - Krevvata, M.
AU - DeAngelis, N.
AU - Heuck, C.
AU - Van Rampelbergh, R.
AU - Kudva, A.
AU - Kobos, R.
AU - Qi, M.
AU - Bahlis, N.J.
JO - Blood advances
PY - 2022
VL - 139
TODO - 4
SP - 492-501
PB - Elsevier B.V.
SN - null
TODO - 10.1182/blood.2020010439
TODO - 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
TODO - 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
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