Daratumumab-bortezomib-thalidomide-dexamethasone for newly diagnosed myeloma: CASSIOPEIA minimal residual disease results

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.

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Journal
Blood
Published
2025-03-24
DOI
https://doi.org/10.1182/blood.2024027620
Citations
17
Primary Topic
Multiple Myeloma Research and Treatments
Type
article
Field-Weighted Citation Impact
30.09

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article

Daratumumab-bortezomib-thalidomide-dexamethasone for newly diagnosed myeloma: CASSIOPEIA minimal residual disease results

Pieter Sonneveld, Thomas Filleron, Véronique Vanquickelberghe, Thomas Dejoie et al.
17 citations
Blood
Multiple Myeloma Research and Treatments
30.09
article

Daratumumab-bortezomib-thalidomide-dexamethasone for newly diagnosed myeloma: CASSIOPEIA minimal residual disease results

Pieter Sonneveld, Thomas Filleron, Véronique Vanquickelberghe, Thomas Dejoie, Thierry T.F. Facon, Jill Corre, Bastien Cabarrou, Niels W.C.J. van de Donk, Winnie Hua, Carla de Boer, Jérôme Lambert, Xavier P Leleu, Fredrik Borgsten, Soraya Wuillème, Richard G. Carson, Marie C. Béné, Annemiek Broijl, Margaret Macro, Denis Caillot, Laure Vincent, Sabrina Mahéo, Aurore Perrot, Sonja Zweegman, Maria Krevvata, Benjamin Hébraud, Cyrille Hulin, Jianping Wang, Michel Delforge, Philippe Moreau, Alba Tuozzo, Melissa Rowe
article en
17 citations

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.

BloodVol. 146(6)
RTX (United States) (US), Johnson & Johnson (United States) (US), Inserm (FR), Université Fédérale de Toulouse Midi-Pyrénées (FR), Université de Lille (FR), Hotel Dieu Hospital (CA), Centre Hospitalier Universitaire de Lille (FR), Centre Hospitalier Universitaire de Nantes (FR), Centre Hospitalier Universitaire de Toulouse (FR), Centre Hospitalier Universitaire de Montpellier (FR), Institut universitaire du cancer de Toulouse Oncopole (FR), Springhouse (US), Amsterdam Neuroscience (NL), Centre Hospitalier Universitaire de Poitiers (FR), Institut de Cancérologie de Bourgogne (FR), Centre Hospitalier Universitaire de Caen Normandie (FR), Hôpital Cardiologique du Haut-Lévêque (FR), Adams Business Associates (United Kingdom) (GB), Institut Claudius Regaud (FR), Hôtel-Dieu de Paris (FR), Johnson & Johnson (Israel) (IL), Hôpital Saint-Louis (FR), Erasmus MC Cancer Institute (NL), Amsterdam University Medical Centers (NL), Laboratoire de Génétique Cellulaire (FR), Johnson & Johnson (Netherlands) (NL), Vrije Universiteit Amsterdam (NL), University of Amsterdam (NL), Cytel (United States) (US), Nantes Université (FR), KU Leuven (BE)
Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Sanofi, Yale University, Celgene, Servier, Kite Pharma
Partnerships for the goals
Openalex Percentile: Top 0%
Multiple Myeloma Research and Treatments
30.09
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