Titre :

Bortezomib, thalidomide, and dexamethasone with or without daratumumab and followed by daratumumab maintenance or observation in transplant-eligible newly diagnosed multiple myeloma: long-term follow-up of the CASSIOPEIA randomised controlled phase 3 trial

Auteur(s) :

Moreau, Philippe [Auteur]
CEA Cadarache
Hulin, Cyrille [Auteur]
Centre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
Perrot, Aurore [Auteur]
Institut Universitaire du Cancer de Toulouse - Oncopole [IUCT Oncopole - UMR 1037]
Arnulf, Bertrand [Auteur]
Service d'hématologie biologique
Belhadj, Karim [Auteur]
CHU Henri Mondor [Créteil]
Benboubker, Lotfi [Auteur]
Centre Hospitalier Régional Universitaire de Tours [CHRU Tours]
Zweegman, Sonja [Auteur]
Amsterdam University Medical Centers [Amsterdam UMC]
Caillon, Hélène [Auteur]
Centre Hospitalier Universitaire de Nantes = Nantes University Hospital [CHU Nantes]
Caillot, Denis [Auteur]
Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand [CHU Dijon]
Avet-Loiseau, Hervé [Auteur]
Institut Universitaire du Cancer de Toulouse - Oncopole [IUCT Oncopole - UMR 1037]
Delforge, Michel [Auteur]
University Hospitals Leuven [Leuven]
Dejoie, Thomas [Auteur]
Centre Hospitalier Universitaire de Nantes = Nantes University Hospital [CHU Nantes]
Facon, Thierry [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Sonntag, Cécile [Auteur]
Hôpital de Hautepierre [Strasbourg]
Fontan, Jean [Auteur]
Service d'hématologie
Mohty, Mohamad [Auteur]
Centre de Recherche Saint-Antoine [CRSA]
Jie, Kon-Siong [Auteur]
Karlin, Lionel [Auteur]
Immuno-Biologie des Lymphomes [CIRI] [CIRI-LIB]
Centre Hospitalier Lyon Sud [CHU - HCL] [CHLS]
Kuhnowski, Frédérique [Auteur]
Institut Curie [Paris]
Lambert, Jérôme [Auteur]
Hopital Saint-Louis [AP-HP] [AP-HP]
Epidemiology and Clinical Statistics for Tumor, Respiratory, and Resuscitation | Epidémiologie Clinique, STatistique, pour la Recherche en Santé [ECSTRRA [CRESS - U1153 / UMR_A 1125]]
Leleu, Xavier [Auteur]
Centre hospitalier universitaire de Poitiers = Poitiers University Hospital [CHU de Poitiers [La Milétrie]]
Macro, Margaret [Auteur]
CHU Caen
Orsini-Piocelle, Frédérique [Auteur]
Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois]
Roussel, Murielle [Auteur]
Hôpital Dupuytren [CHU Limoges]
Schiano de Colella, Jean Marc [Auteur]
Institut Paoli-Calmettes [IPC]
van de Donk, Niels Wcj [Auteur]
Vrije Universiteit Amsterdam [Amsterdam] [VU]
Wuillème, Soraya [Auteur]
Centre Hospitalier Universitaire de Nantes = Nantes University Hospital [CHU Nantes]
Broijl, Annemiek [Auteur]
Erasmus University Medical Center [Rotterdam] [Erasmus MC]
Touzeau, Cyrille [Auteur]
Hôtel-Dieu de Nantes
Tiab, Mourad [Auteur]
Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon [CHD Vendée]
Marolleau, Jean-Pierre [Auteur]
HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 [HEMATIM]
Laboratoire d'Hématologie [CHU Amiens]
Meuleman, Nathalie [Auteur]
Institut Jules Bordet [Bruxelles]
Vekemans, Marie-Christiane [Auteur]
Cliniques Universitaires Saint-Luc [Bruxelles]
Westerman, Matthijs [Auteur]
Klein, Saskia [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Levin, Mark-David [Auteur]
Offner, Fritz [Auteur]
Ghent University Hospital
Escoffre-Barbe, Martine [Auteur]
Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
Eveillard, Jean-Richard [Auteur]
Hôpital Morvan - CHRU de Brest [CHU - BREST ]
Garidi, Réda [Auteur]
Hua, Winnie [Auteur]
Wang, Jianping [Auteur]
Janssen Research & Development
Tuozzo, Alba [Auteur]
Janssen Research & Development
de Boer, Carla [Auteur]
Janssen Research & Development
Rowe, Melissa [Auteur]
Janssen Research & Development
Vanquickelberghe, Veronique [Auteur]
Janssen Research & Development
Carson, Robin [Auteur]
Janssen Research & Development
Vermeulen, Jessica [Auteur]
Janssen Research & Development
Corre, Jill [Auteur]
Institut Universitaire du Cancer de Toulouse - Oncopole [IUCT Oncopole - UMR 1037]
Sonneveld, Pieter [Auteur]
Erasmus University Medical Center [Rotterdam] [Erasmus MC]

Titre de la revue :

Lancet Oncology

Pagination :

1003-1014

Éditeur :

Elsevier

Date de publication :

2024-06

ISSN :

1470-2045

Mot(s)-clé(s) en anglais :

STEM-CELL TRANSPLANTATION
OPEN-LABEL
ANTIBODY DARATUMUMAB
THERAPY
LENALIDOMIDE
MONOTHERAPY
CRITERIA
CD38

Discipline(s) HAL :

Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Hématologie
Sciences du Vivant [q-bio]/Cancer

Résumé en anglais : [en]

BackgroundCASSIOPEIA part 1 demonstrated superior depth of response and prolonged progression-free survival with daratumumab in combination with bortezomib, thalidomide, and dexamethasone (D-VTd) versus bortezomib, ...
Lire la suite >BackgroundCASSIOPEIA part 1 demonstrated superior depth of response and prolonged progression-free survival with daratumumab in combination with bortezomib, thalidomide, and dexamethasone (D-VTd) versus bortezomib, thalidomide, and dexamethasone (VTd) alone as an induction and consolidation regimen in transplant-eligible patients newly diagnosed with myeloma. In CASSIOPEIA part 2, daratumumab maintenance significantly improved progression-free survival and increased minimal residual disease (MRD)-negativity rates versus observation. Here, we report long-term study outcomes of CASSIOPEIA.MethodsCASSIOPEIA was a two-part, open-label, phase 3 trial of patients done at 111 European academic and community-based centres. Eligible patients were aged 18–65 years with transplant-eligible newly diagnosed myeloma and an Eastern Cooperative Oncology Group performance status of 0–2. In part 1, patients were randomly assigned (1:1) to pre-transplant induction and post-transplant consolidation with D-VTd or VTd. Patients who completed consolidation and had a partial response or better were re-randomised (1:1) to intravenous daratumumab maintenance (16 mg/kg every 8 weeks) or observation for 2 years or less. An interactive web-based system was used for both randomisations, and randomisation was balanced using permuted blocks of four. Stratification factors for the first randomisation (induction and consolidation phase) were site affiliation, International Staging System disease stage, and cytogenetic risk status. Stratification factors for the second randomisation (maintenance phase) were induction treatment and depth of response in the induction and consolidation phase. The primary endpoint for the induction and consolidation phase was the proportion of patients who achieved a stringent complete response after consolidation; results for this endpoint remain unchanged from those reported previously. The primary endpoint for the maintenance phase was progression-free survival from second randomisation. Efficacy evaluations in the induction and consolidation phase were done on the intention-to-treat population, which included all patients who underwent first randomisation, and efficacy analyses in the maintenance phase were done in the maintenance-specific intention-to-treat population, which included all patients who were randomly assigned at the second randomisation. This analysis represents the final data cutoff at the end of the study. The trial is registered with ClinicalTrials.gov, NCT02541383.FindingsBetween Sept 22, 2015 and Aug 1, 2017, 1085 patients were randomly assigned to D-VTd (n=543) or VTd (n=542); between May 30, 2016 and June 18, 2018, 886 were re-randomised to daratumumab maintenance (n=442) or observation (n=444). At the clinical cutoff date, Sept 1, 2023, median follow-up was 80·1 months (IQR 75·7–85·6) from first randomisation and 70·6 months (66·4–76·1) from second randomisation. Progression-free survival from second randomisation was significantly longer in the daratumumab maintenance group than the observation-alone group (median not reached [95% CI 79·9–not estimable (NE)] vs 45·8 months [41·8–49·6]; HR 0·49 [95% CI 0·40–0·59]; p<0·0001); benefit was observed with D-VTd with daratumumab maintenance versus D-VTd with observation (median not reached [74·6–NE] vs 72·1 months [52·8–NE]; 0·76 [0·58–1·00]; p=0·048) and VTd with daratumumab maintenance versus VTd with observation (median not reached [66·9–NE] vs 32·7 months [27·2–38·7]; 0·34 [0·26–0·44]; p<0·0001).InterpretationThe long-term follow-up results of CASSIOPEIA show that including daratumumab in both the induction and consolidation phase and the maintenance phase led to superior progression-free survival outcomes. Our results confirm D-VTd induction and consolidation as a standard of care, and support the option of subsequent daratumumab monotherapy maintenance, for transplant-eligible patients with newly diagnosed multiple myeloma.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277

Source :

Harvested from HAL