Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma

Pieter Sonneveld*, Meletios A Dimopoulos, Mario Boccadoro, Hang Quach, P Joy Ho, Meral Beksac, Cyrille Hulin, Elisabetta Antonioli, Xavier Leleu, Silvia Mangiacavalli, Aurore Perrot, Michele Cavo, Angelo Belotti, Annemiek Broijl, Francesca Gay, Roberto Mina, Inger S Nijhof, Niels W C J van de Donk, Eirini Katodritou, Fredrik SchjesvoldAnna Sureda Balari, Laura Rosiñol, Michel Delforge, Wilfried Roeloffzen, Tobias Silzle, Annette Vangsted, Hermann Einsele, Andrew Spencer, Roman Hajek, Artur Jurczyszyn, Sarah Lonergan, Tahamtan Ahmadi, Yanfang Liu, Jianping Wang, Diego Vieyra, Emilie M J van Brummelen, Veronique Vanquickelberghe, Anna Sitthi-Amorn, Carla J de Boer, Robin Carson, Paula Rodriguez-Otero, Joan Bladé, Philippe Moreau, PERSEUS Trial Investigators

*Corresponding author af dette arbejde

Abstract

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.).

OriginalsprogEngelsk
TidsskriftThe New England journal of medicine
Vol/bind390
Udgave nummer4
Sider (fra-til)301-313
Antal sider13
ISSN0028-4793
DOI
StatusUdgivet - 25 jan. 2024

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