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
- Type de publi. : Article dans une revue
- Date de publi. : 01/06/2024
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Auteurs :
Philippe MoreauCyrille HulinAurore PerrotBertrand ArnulfKarim BelhadjLotfi BenboubkerSonja ZweegmanHélène CaillonDenis CaillotHervé Avet-LoiseauMichel DelforgeThomas DejoieThierry FaconCécile SonntagJean FontanMohamad MohtyKon-Siong JieLionel KarlinFrédérique KuhnowskiJérôme LambertXavier LeleuMargaret MacroFrédérique Orsini-PiocelleMurielle RousselJean Marc Schiano de ColellaNiels Wcj van de DonkSoraya WuillèmeAnnemiek BroijlCyrille TouzeauMourad TiabJean-Pierre MarolleauNathalie MeulemanMarie-Christiane VekemansMatthijs WestermanSaskia KleinMark-David LevinFritz OffnerMartine Escoffre-BarbeJean-Richard EveillardRéda GaridiWinnie HuaJianping WangAlba TuozzoCarla de BoerMelissa RoweVeronique VanquickelbergheRobin CarsonJessica VermeulenJill CorrePieter Sonneveld
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Organismes :
CEA Cadarache
Centre Hospitalier Universitaire de Bordeaux
Institut Universitaire du Cancer de Toulouse - Oncopole
Service d'hématologie biologique
CHU Henri Mondor [Créteil]
Centre Hospitalier Régional Universitaire de Tours
Amsterdam University Medical Centers
Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
Institut Universitaire du Cancer de Toulouse - Oncopole
Universitair Ziekenhuis Leuven = University Hospital of Leuven = Hopital universitaire de Louvain
Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277
Hôpital de Hautepierre [Strasbourg]
Service d'hématologie
Centre de Recherche Saint-Antoine
Zuyderland Hospital [Heerlen, The Netherlands]
Centre Hospitalier Lyon Sud [CHU - HCL]
Immuno-Biologie des Lymphomes [CIRI]
Institut Curie [Paris]
Epidemiology and Clinical Statistics for Tumor, Respiratory, and Resuscitation | Epidémiologie Clinique, STatistique, pour la Recherche en Santé
Hopital Saint-Louis [AP-HP]
Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
CHU Caen Normandie – Centre Hospitalier Universitaire de Caen Normandie
Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois]
Hôpital Dupuytren [CHU Limoges]
Institut Paoli-Calmettes
Vrije Universiteit Amsterdam [Amsterdam]
Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
Erasmus University Medical Center [Rotterdam]
Hôtel-Dieu de Nantes
Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon
Service d'Hématologie Clinique et Thérapie Cellulaire [CHU Amiens]
HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666
Institut Jules Bordet [Bruxelles]
Cliniques Universitaires Saint-Luc [Bruxelles]
Medical Center Alkmaar
University Medical Center Groningen [Groningen]
Albert Schweitzer Hospital
Ghent University Hospital
Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
Hôpital Morvan - CHRU de Brest
Janssen Research & Development
Janssen Research & Development
Janssen Research & Development
Janssen Research & Development
Janssen Research & Development
Janssen Research & Development
Janssen Research & Development
Institut Universitaire du Cancer de Toulouse - Oncopole
Erasmus University Medical Center [Rotterdam]
- Publié dans Lancet Oncology le 02/11/2020
Résumé : Background CASSIOPEIA 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. Methods CASSIOPEIA 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 . Findings Between 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). Interpretation The 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.
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