Publicaciones científicas
Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma
Pieter Sonneveld 1 , Meletios A Dimopoulos 1 , Mario Boccadoro 1 , Hang Quach 1 , P Joy Ho 1 , Meral Beksac 1 , Cyrille Hulin 1 , Elisabetta Antonioli 1 , Xavier Leleu 1 , Silvia Mangiacavalli 1 , Aurore Perrot 1 , Michele Cavo 1 , Angelo Belotti 1 , Annemiek Broijl 1 , Francesca Gay 1 , Roberto Mina 1 , Inger S Nijhof 1 , Niels W C J van de Donk 1 , Eirini Katodritou 1 , Fredrik Schjesvold 1 , Anna Sureda Balari 1 , Laura Rosiñol 1 , Michel Delforge 1 , Wilfried Roeloffzen 1 , Tobias Silzle 1 , Annette Vangsted 1 , Hermann Einsele 1 , Andrew Spencer 1 , Roman Hajek 1 , Artur Jurczyszyn 1 , Sarah Lonergan 1 , Tahamtan Ahmadi 1 , Yanfang Liu 1 , Jianping Wang 1 , Diego Vieyra 1 , Emilie M J van Brummelen 1 , Veronique Vanquickelberghe 1 , Anna Sitthi-Amorn 1 , Carla J de Boer 1 , Robin Carson 1 , Paula Rodriguez-Otero 1 , Joan Bladé 1 , Philippe Moreau 1 ; PERSEUS Trial Investigators
Background: Daratumumab, a monoclonal antibody targeting CD38, has been approved for use with standard myeloma regimens. An evaluation of subcutaneous daratumumab combined with bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of transplantation-eligible patients with newly diagnosed multiple myeloma is needed.
Methods: In this phase 3 trial, we randomly assigned 709 transplantation-eligible patients with newly diagnosed multiple myeloma to receive either subcutaneous daratumumab combined with VRd induction and consolidation therapy and with lenalidomide maintenance therapy (D-VRd group) or VRd induction and consolidation therapy and lenalidomide maintenance therapy alone (VRd group). The primary end point was progression-free survival. Key secondary end points were a complete response or better and minimal residual disease (MRD)-negative status.
Results: At a median follow-up of 47.5 months, the risk of disease progression or death in the D-VRd group was lower than the risk in the VRd group. The estimated percentage of patients with progression-free survival at 48 months was 84.3% in the D-VRd group and 67.7% in the VRd group (hazard ratio for disease progression or death, 0.42; 95% confidence interval, 0.30 to 0.59; P<0.001); the P value crossed the prespecified stopping boundary (P = 0.0126). The percentage of patients with a complete response or better was higher in the D-VRd group than in the VRd group (87.9% vs. 70.1%, P<0.001), as was the percentage of patients with MRD-negative status (75.2% vs. 47.5%, P<0.001). Death occurred in 34 patients in the D-VRd group and 44 patients in the VRd group. Grade 3 or 4 adverse events occurred in most patients in both groups; the most common were neutropenia (62.1% with D-VRd and 51.0% with VRd) and thrombocytopenia (29.1% and 17.3%, respectively). Serious adverse events occurred in 57.0% of the patients in the D-VRd group and 49.3% of those in the VRd group.
Conclusions: The addition of subcutaneous daratumumab to VRd induction and consolidation therapy and to lenalidomide maintenance therapy conferred a significant benefit with respect to progression-free survival among transplantation-eligible patients with newly diagnosed multiple myeloma. (Funded by the European Myeloma Network in collaboration with Janssen Research and Development; PERSEUS ClinicalTrials.gov number, NCT03710603; EudraCT number, 2018-002992-16.).
CITA DEL ARTÍCULO N Engl J Med. 2023 Dec 12. doi: 10.1056/NEJMoa2312054
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