Daratumumab-bortezomib-thalidomide-dexamethasone for newly diagnosed myeloma: CASSIOPEIA minimal residual disease results
Jill Corre, Laure Vincent, Philippe Moreau, Benjamin Hébraud, Cyrille Hulin, Marie C. Béné, Annemiek Broijl, Denis Caillot, Michel Delforge, Thomas Dejoie, Thierry Façon, Jérôme Lambert, Xavier Leleu, Margaret Macro, Aurore Perrot, Sonja Zweegman, Thomas Filleron, Bastien Cabarrou, Niels W.C.J. van de Donk, Sabrina Mahéo, Winnie Hua, Jianping Wang, Maria Krevvata, Véronique Vanquickelberghe, Carla de Boer, Alba Tuozzo, Fredrik Borgsten, Melissa Rowe, Robin Carson, Soraya Wuillème, Pieter Sonneveld
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.