Daratumumab-bortezomib-thalidomide-dexamethasone for newly diagnosed myeloma: CASSIOPEIA minimal residual disease results
Abstract
Abstract Previous results from CASSIOPEIA demonstrated superior progression-free survival (PFS) and minimal residual disease (MRD) negativity with the addition of daratumumab to bortezomib, thalidomide, and dexamethasone (VTd) induction/consolidation and with daratumumab maintenance vs observation in transplant-eligible, newly diagnosed multiple myeloma. Here, we present long-term MRD status and PFS outcomes after a median follow-up of 80.1 months. Patients were randomly assigned (1:1) to daratumumab plus VTd (D-VTd) or VTd induction/consolidation; patients remaining on study were rerandomized to daratumumab maintenance or observation for ≤2 years. MRD status was assessed at predefined time points during each study phase. D-VTd improved overall MRD-negativity rates (10–5) after induction (34.6% vs 23.1%) and consolidation (63.7% vs 43.7%) and provided PFS benefit, regardless of postinduction MRD status, vs VTd alone. Daratumumab maintenance improved overall MRD-negativity rates over observation, regardless of induction/consolidation treatment (D-VTd/daratumumab vs D-VTd/observation, 10–5 [77.3% vs 70.7%] and 10–6 [60.7% vs 52.0%]; VTd/daratumumab vs VTd/observation, 10–5 [70.9% vs 51.2%] and 10–6 [48.4% vs 30.7%]) and improved MRD-negativity rates, regardless of risk status, as defined by cytogenetic abnormalities or the revised International Staging System score. Furthermore, daratumumab maintenance provided PFS benefit vs observation, regardless of induction/consolidation treatment and postconsolidation MRD status. D-VTd followed by daratumumab maintenance consistently produced the highest landmark, cumulative, and sustained MRD-negativity rates (10–5 and 10–6), translating to superior long-term PFS outcomes. These results demonstrate that daratumumab-based induction/consolidation followed by daratumumab maintenance resulted in the deepest and most durable MRD negativity, leading to superior PFS outcomes. This trial was registered at www.clinicaltrials.gov as #NCT02541383.
Article Details
Authors (31)
Jill Corre
Unité Génomique du Myélome, Hôpital Universitaire de Toulouse Oncopole, Université de Toulouse, Toulouse, France
Laure Vincent
11Department of Hematology, Montpellier University Hospital, Montpellier, France
Philippe Moreau
Benjamin Hebraud
2Institut Universitaire du Cancer, CHU Toulouse, Toulouse, France
Cyrille Hulin
Service d’Hématologie, Hôpital Haut Lévêque, Centre Hospitalier Universitaire (CHU) de Bordeaux, Pessac, France
Marie C. Béné
11Department of Hematology, Centre Hospitalier Universitaire de Nantes, Nantes, France
Annemiek Broijl
1Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
Denis Caillot
6Department of Hematology, Centre Hospitalier Universitaire Dijon, Hôpital Du Bocage, Dijon, France
Michel Delforge
Thomas Dejoie
10Biochemistry Laboratory, Nantes University Hospital, Nantes, France
Thierry Facon
6Department of Hematology, University Hospital and INSERM Unité Mixte de Recherche S1277, Lille, France
Jérôme Lambert
Biostatistics and Medical Information Department, Hôpital St. Louis, Paris
Xavier Leleu
Service Hématologie, Hôpital Universitaire de Poitiers, Poitiers, France
Margaret Macro
Service Hématologie, Institut Hématologie de Basse Normandie, Hôpital Universitaire de Caen, Caen, France
Aurore Perrot
Sonja Zweegman
Thomas Filleron
16Biostatistics and Health Data Science Unit, Oncopole Claudius Regaud, Institut Universitaire du Cancer Oncopole, Toulouse, France
Bastien Cabarrou
16Biostatistics and Health Data Science Unit, Oncopole Claudius Regaud, Institut Universitaire du Cancer Oncopole, Toulouse, France
Niels W. C. J. van de Donk
Sabrina Mahéo
IUCT, TOULOUSE, France
Winnie Hua
17Cytel Inc, Waltham, MA
Jianping Wang
Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering
Maria Krevvata
Johnson & Johnson, Spring House, PA
Veronique Vanquickelberghe
Johnson & Johnson, Beerse, Belgium
Carla de Boer
20Johnson & Johnson, Leiden, The Netherlands
Alba Tuozzo
18Johnson & Johnson, Spring House, PA
Fredrik Borgsten
21Johnson & Johnson, Raritan, NJ
Melissa Rowe
Robin Carson
Johnson & Johnson, Spring House, PA
Soraya Wuilleme
6Hematology Biology, University Hospital Hôtel-Dieu, Nantes, France
Pieter Sonneveld