Consolidation and Maintenance in Newly Diagnosed Multiple Myeloma

Pieter Sonneveld*, Meletios A. Dimopoulos, Meral Beksac, Bronno van der Holt, Sara Aquino, Heinz Ludwig, Sonja Zweegman, Thilo Zander, Elena Zamagni, Ruth Wester, Roman Hajek, Lucia Pantani, Luca Dozza, Francesca Gay, Anne Maria Cafro, Luca De Rosa, Annamaria Morelli, Henrik Gregersen, Nina Gulbrandsen, Petra CornelisseRosella Troia, Stefania Oliva, Vincent van de Velden, Ka Lung Wu, Paula F. Ypma, Gerard Bos, Mark David Levin, Luca Pour, Christoph Driessen, Annemiek Broijl, Alexandra Croockewit, Monique C. Minnema, Anders Waage, Cecilie Hveding, Niels W.C.J. van de Donk, Massimo Offidani, Giuseppe A. Palumbo, Andrew Spencer, Mario Boccadoro, Michele Cavo

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Scopus)

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] 5 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 VRDtreated 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.

Original languageEnglish
Pages (from-to)3613-3622
Number of pages10
JournalJournal of Clinical Oncology
Volume39
Issue number32
Early online date14 Sep 2021
DOIs
Publication statusPublished - 10 Nov 2021

Bibliographical note

Funding Information:
Supported by the Dutch Cancer Society (grant 2010-4798), by the European Myeloma Network, and by unrestricted grants from Celgene and Janssen.

Funding Information:
Funding for this study was provided by the Dutch National Cancer Society and by Janssen and Celgene. The study was performed as an independent, investigator-sponsored study. All patients provided written informed consent and the study was approved by the independent ethics committee or institutional review board of each participating hospital. Funders had no role in study design, data collection, data analysis, data interpretation, or manuscript writing. The corresponding author had full access to the data and carried the final responsibility for the submission of the manuscript.

Publisher Copyright:
© 2021 by American Society of Clinical Oncology.

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