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Consolidation and Maintenance in Newly Diagnosed Multiple Myeloma

P. Sonneveld, MA. Dimopoulos, M. Beksac, B. van der Holt, S. Aquino, H. Ludwig, S. Zweegman, T. Zander, E. Zamagni, R. Wester, R. Hajek, L. Pantani, L. Dozza, F. Gay, A. Cafro, L. De Rosa, A. Morelli, H. Gregersen, N. Gulbrandsen, P. Cornelisse,...

. 2021 ; 39 (32) : 3613-3622. [pub] 20210914

Language English Country United States

Document type Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc22003212

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.

Albert Schweitzer Ziekenhuis Dordrecht the Netherlands

ASST Grande Ospedale Metropolitano Niguarda Milan Italy

Clinica di Ematologia AOU Ospedali Riuniti di Ancona Ancona Italy

Department of Clinical Therapeutics School of Medicine National and Kapodistrian University of Athens Athens Greece

Department of Experimental Diagnostic and Experimental Medicine Seràgnoli Institute of Hematology Bologna University School of Medicine S Orsola Malpighi Hospital Bologna Italy

Department of Haematology Aalborg University Hospital Aalborg Denmark

Department of Haematology Alfred Hospital Monash University Melbourne Australia

Department of Hematology Amsterdam UMC Cancer Center Amsterdam Vrije Universiteit Amsterdam Amsterdam the Netherlands

Department of Hematology Ankara University School of Medicine Ankara Turkey

Department of Hematology Erasmus MC Cancer Institute Rotterdam the Netherlands

Department of Hematology Haga Ziekenhuis The Hague the Netherlands

Department of Hematology HOVON Data Center Erasmus MC Cancer Institute Rotterdam the Netherlands

Department of Hematology Oslo University Hospital Oslo Norway

Department of Hematology Radboud University Medical Centre Nijmegen the Netherlands

Department of Hematology St Olav Hospital Trondheim Norway

Department of Hematology Transfusion Medicine and Biotechnology Santo Spirito Civic Hospital Pescara Italy

Department of Hematology University Medical Centre Utrecht the Netherlands

Department of Hematology ZNA Stuivenberg Antwerp Belgium

Department of Immunology Erasmus MC Cancer Institute Rotterdam the Netherlands

Department of Oncology Hematology Kantonsspital St Gallen Switzerland

Department of Scienze Mediche Chirurgiche e Tecnologie Avanzate G F Ingrassia University of Catania Catania Italy

HOVON Data Center Erasmus MC Cancer Institute Rotterdam the Netherlands

IRCCS Azienda Ospedaliera Universitaria San Martino IST Instituto Nazionale per la Ricerca sul Cancro Genova Italy

IRCCS Azienda Ospedaliero Universitaria di Bologna Istituto di Ematologia Seràgnoli and Dipartimento di Medicina Specialistica Diagnostica e Sperimentale Università di Bologna Bologna Italy

IRCCS Azienda Ospedaliero Universitaria di Bologna Istituto di Ematologia Seràgnoli Bologna Italy

IRCCS S Orsola Malpighi Istituto di Ematologia Seràgnoli Dipartimento di Medicina Specialistica Diagnostica e Sperimentale Università degli Studi di Bologna Bologna Italy

Maastricht University Medical Center Maastricht the Netherlands

Medical Oncology Luzerner Kantonshospital Luzern Switzerland

Myeloma Unit Division of Hematology University of Torino Azienda Ospedaliero Universitaria Città della Salute e della Scienza Torino Italy

Ospedale San Camillo Forlanini Rome Italy

Sahlgrenska University Hospital Gothenburg Sweden

University Hospital Brno Brno Czech Republic

University Hospital Ostrava Ostrava Czech Republic

Wilhelminen Cancer Research Institute c o Wilhelminenspital Vienna Austria

References provided by Crossref.org

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$a 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.
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