@article{3032691,
    title = "Consolidation and Maintenance in Newly Diagnosed Multiple Myeloma",
    author = "Sonneveld, Pieter and Dimopoulos, Meletios A. and Beksac, Meral and van and der Holt, Bronno and Aquino, Sara and Ludwig, Heinz and Zweegman, Sonja and and Zander, Thilo and Zamagni, Elena and Wester, Ruth and Hajek, Roman and and Pantani, Lucia and Dozza, Luca and Gay, Francesca and Cafro, and AnneMaria and De Rosa, Luca and Morelli, Annamaria and Gregersen, Henrik and and Gulbrandsen, Nina and Cornelisse, Petra and Troia, Rosella and and Oliva, Stefania and van de Velden, Vincent and Wu, KaLung and Ypma, and Paula F. and Bos, Gerard and Levin, Mark-David and Pour, Luca and and Driessen, Christoph and Broijl, Annemiek and Croockewit, Alexandra and and Minnema, Monique C. and Waage, Anders and Hveding, Cecilie and van de and Donk, Niels W. C. J. and Offidani, Massimo and Palumbo, Giuseppe A. and and Spencer, Andrew and Boccadoro, Mario and Cavo, Michele",
    journal = "Journal of Clinical Oncology",
    year = "2021",
    volume = "39",
    number = "32",
    pages = "3613+",
    publisher = "Lippincott, Williams & Wilkins",
    issn = "0732-183X, 1527-7755",
    doi = "10.1200/JCO.21.01045",
    abstract = "PURPOSE To address the role of consolidation treatment for newly
diagnosed, transplant eligible patients with multiple myeloma in a
controlled clinical trial.
PATIENTS AND METHODS The EMN02/HOVON95 trial compared consolidation
treatment with two cycles of bortezomib, lenalidomide, and dexamethasone
(VRD) or no consolidation after induction and intensification therapy,
followed by continuous lenalidomide maintenance. Primary study end point
was progression-free survival (PFS).
RESULTS Eight hundred seventy-eight eligible patients were randomly
assigned to receive VRD consolidation (451 patients) or no consolidation
(427 patients). At a median follow-up of 74.8 months, median PFS with
adjustment for pretreatment was prolonged in patients randomly assigned
to VRD consolidation (59.3 v 42.9 months, hazard ratio [HR] = 0.81;
95% CI, 0.68 to 0.96; P = .016). The PFS benefit was observed across
most predefined subgroups, including revised International Staging
System (ISS) stage, cytogenetics, and prior treatment. Revised ISS3
stage (HR, 2.00; 95% CI, 1.41 to 2.86) and ampl1q (HR, 1.67; 95% CI,
1.37 to 2.04) were significant adverse prognostic factors. The median
duration of maintenance was 33 months (interquartile range 13-86
months). Response complete response (CR) after consolidation versus no
consolidation before start of maintenance was 34% versus 18%,
respectively (P < .001). Response >= CR on protocol including
maintenance was 59% with consolidation and 46% without (P < .001).
Minimal residual disease analysis by flow cytometry in a subgroup of 226
patients with CR or stringent complete response or very good partial
response before start of maintenance demonstrated a 74% minimal
residual disease-negativity rate in VRD-treated patients. Toxicity from
VRD was acceptable and manageable.
CONCLUSION Consolidation treatment with VRD followed by lenalidomide
maintenance improves PFS and depth of response in newly diagnosed
patients with multiple myeloma as compared to maintenance alone. (C)
2021 by American Society of Clinical Oncology"
}