학술논문
Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study.
Document Type
Academic Journal
Author
Moreau P; Hematology, University Hospital Hôtel-Dieu, Nantes, France. Electronic address: philippe.moreau@chu-nantes.fr.; Attal M; Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France.; Hulin C; Department of Hematology, Hopital Haut Leveque, University Hospital Bordeaux, Bordeaux, France.; Arnulf B; Immuno-Hématologie, Hopital Saint Louis, Paris, France.; Belhadj K; Hematology, Hopital Henri Mondor, Creteil, France.; Benboubker L; Hôpital de Bretonneau, Centre Hospitalier Régional Universitaire de Tours, Tours, France.; Béné MC; Hematology Biology, University Hospital Hôtel Dieu, Nantes, France.; Broijl A; Erasmus University Medical Center Cancer Institute, Rotterdam, Netherlands.; Caillon H; Biochemistry Laboratory, Hospital of Nantes, Nantes, France.; Caillot D; Hôpital Du Bocage, Centre Hospitalier Universitaire Dijon, Dijon, France.; Corre J; Unite de Genomique du Myelome, Institut universitaire du cancer de Toulouse Oncopole, Toulouse, France.; Delforge M; Universitaire Ziekenhuizen Leuven, Leuven, Belgium.; Dejoie T; Biochemistry Laboratory, Hospital of Nantes, Nantes, France.; Doyen C; Centre Hospitalier Universitaire UCL Namur-site Godinne, Yvoir, Belgium.; Facon T; Service des Maladies du Sang, Hôpital Claude Huriez, Lille, France.; Sonntag C; Hopital Hautepierre, Strasbourg, France.; Fontan J; Jean Minjoz Hôpital, Besancon, France.; Garderet L; Team Proliferation and Differentiation of Stem Cells, Centre de Recherche Saint-Antoine, Inserm, Sorbonne Université, Paris, France; Département d'Hématologie et de Thérapie Cellulaire, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France.; Jie KS; Zuyderland Medisch Centrum, Sittard, Netherlands.; Karlin L; Service d'Hématologie Clinique, Centre Hospitalier Lyon-Sud, Lyon, France.; Kuhnowski F; Institut Curie Paris, Paris, France.; Lambert J; Biostatistical Department, Hôpital Saint Louis, Paris, France.; Leleu X; Hôpital la Milétrie, Centre Hospitalier Universitaire de Poitiers, Poitiers, France.; Lenain P; Centre de Lutte Contre le Cancer-Centre Henri Becquerel, Rouen, France.; Macro M; Centre Hospitalier Universitaire de Caen, Caen, France.; Mathiot C; Institut Français de la Mode, Paris, France.; Orsini-Piocelle F; Centre Hospitalier Annecy Genevois, Pringy, France.; Perrot A; Hematology Department, Vandoeuvre Les Nancy, University Hospitals Nancy, France.; Stoppa AM; Institut Paoli Calmettes, Marseille, France.; van de Donk NW; Department of Hematology, University Medical Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.; Wuilleme S; Hematology Biology, University Hospital Hôtel Dieu, Nantes, France.; Zweegman S; Department of Hematology, University Medical Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.; Kolb B; Hôpital Robert Debré, Centre Hospitalier Universitaire de Reims, Reims, France.; Touzeau C; Centre Hospitalier Universitaire de Nantes, Nantes, France.; Roussel M; Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France.; Tiab M; Centre Hospitalier Départemental Vendée, La Roche sur Yon, France.; Marolleau JP; Centre Hospitalier Universitaire Amiens Sud, Amiens, France.; Meuleman N; Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.; Vekemans MC; Cliniques Universitaires Saint-Luc, Brussels, Belgium.; Westerman M; Northwest Clinics, Alkmaar, Netherlands.; Klein SK; Meander Medical Center, Amersfoort, Netherlands.; Levin MD; Albert Schweitzer Hospital, Dordrecht, Netherlands.; Fermand JP; Service d'Immuno-Hématologie, Département d'Immunologie Clinique, Inserm and Intergroupe Francophone du Myélome, Hôpital Saint-Louis, Paris, France.; Escoffre-Barbe M; Hôpital de Pontchaillou, Centre Hospitalier Universitaire de Rennes, Rennes, France.; Eveillard JR; Hôpital A. Morvan, Centre Hospitalier Universitaire de Brest, Brest, France.; Garidi R; Hospital Center de Saint-Quentin, Saint Quentin, France.; Ahmadi T; Genmab US, Inc, Princeton, NJ, USA.; Zhuang S; Janssen Research & Development, Raritan, NJ, USA.; Chiu C; Janssen Research & Development, Spring House, PA, USA.; Pei L; Janssen Research & Development, Raritan, NJ, USA.; de Boer C; Janssen Research & Development, LLC, Leiden, Netherlands.; Smith E; Janssen Research & Development, LLC, High Wycombe, UK.; Deraedt W; Janssen Research & Development, Beerse, Belgium.; Kampfenkel T; Janssen Research & Development, LLC, Leiden, Netherlands.; Schecter J; Janssen Research & Development, Raritan, NJ, USA.; Vermeulen J; Janssen Research & Development, LLC, Leiden, Netherlands.; Avet-Loiseau H; Unite de Genomique du Myelome, Institut universitaire du cancer de Toulouse Oncopole, Toulouse, France.; Sonneveld P; Erasmus University Medical Center Cancer Institute, Rotterdam, Netherlands.
Source
Publisher: Elsevier Country of Publication: England NLM ID: 2985213R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1474-547X (Electronic) Linking ISSN: 01406736 NLM ISO Abbreviation: Lancet Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Bortezomib, thalidomide, and dexamethasone (VTd) plus autologous stem-cell transplantation is standard treatment in Europe for transplant-eligible patients with newly diagnosed multiple myeloma. We evaluated whether the addition of daratumumab to VTd before and after autologous stem-cell transplantation would improve stringent complete response rate in patients with newly diagnosed multiple myeloma.
Methods: In this two-part, randomised, open-label, phase 3 CASSIOPEIA trial, we recruited transplant-eligible patients with newly diagnosed multiple myeloma at 111 European sites. Patients were randomly assigned (1:1) to receive four pre-transplant induction and two post-transplant consolidation cycles of VTd alone (VTd group) or in combination with daratumumab (D-VTd group). The primary endpoint of part 1 was stringent complete response assessed 100 days after transplantation. Part 2 (maintenance) is ongoing. The trial is registered with ClinicalTrials.gov, number NCT02541383.
Findings: Between Sept 22, 2015, and Aug 1, 2017, 1085 patients were enrolled at 111 European sites and were randomly assigned to the D-VTd group (n=543) or the VTd group (n=542). At day 100 after transplantation, 157 (29%) of 543 patients in the D-VTd group and 110 (20%) of 542 patients in the VTd group in the intention-to-treat population had achieved a stringent complete response (odds ratio 1·60, 95% CI 1·21-2·12, p=0·0010). 211 (39%) patients in the D-VTd group versus 141 (26%) in the VTd group achieved a complete response or better, and 346 (64%) of 543 versus 236 (44%) of 542 achieved minimal residual disease-negativity (10-5 sensitivity threshold, assessed by multiparametric flow cytometry; both p<0·0001). Median progression-free survival from first randomisation was not reached in either group (hazard ratio 0·47, 95% CI 0·33-0·67, p<0·0001). 46 deaths on study were observed (14 vs 32, 0·43, 95% CI 0·23-0·80). The most common grade 3 or 4 adverse events were neutropenia (28% vs 15%), lymphopenia (17% vs 10%), and stomatitis (13% vs 16%).
Interpretation: D-VTd before and after autologous stem-cell transplantation improved depth of response and progression-free survival with acceptable safety. CASSIOPEIA is the first study showing the clinical benefit of daratumumab plus standard of care in transplant-eligible patients with newly diagnosed multiple myeloma.
Funding: The Intergroupe Francophone du Myélome and Dutch-Belgian Cooperative Trial Group for Hematology Oncology.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)
Methods: In this two-part, randomised, open-label, phase 3 CASSIOPEIA trial, we recruited transplant-eligible patients with newly diagnosed multiple myeloma at 111 European sites. Patients were randomly assigned (1:1) to receive four pre-transplant induction and two post-transplant consolidation cycles of VTd alone (VTd group) or in combination with daratumumab (D-VTd group). The primary endpoint of part 1 was stringent complete response assessed 100 days after transplantation. Part 2 (maintenance) is ongoing. The trial is registered with ClinicalTrials.gov, number NCT02541383.
Findings: Between Sept 22, 2015, and Aug 1, 2017, 1085 patients were enrolled at 111 European sites and were randomly assigned to the D-VTd group (n=543) or the VTd group (n=542). At day 100 after transplantation, 157 (29%) of 543 patients in the D-VTd group and 110 (20%) of 542 patients in the VTd group in the intention-to-treat population had achieved a stringent complete response (odds ratio 1·60, 95% CI 1·21-2·12, p=0·0010). 211 (39%) patients in the D-VTd group versus 141 (26%) in the VTd group achieved a complete response or better, and 346 (64%) of 543 versus 236 (44%) of 542 achieved minimal residual disease-negativity (10
Interpretation: D-VTd before and after autologous stem-cell transplantation improved depth of response and progression-free survival with acceptable safety. CASSIOPEIA is the first study showing the clinical benefit of daratumumab plus standard of care in transplant-eligible patients with newly diagnosed multiple myeloma.
Funding: The Intergroupe Francophone du Myélome and Dutch-Belgian Cooperative Trial Group for Hematology Oncology.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)