Benefit of Adding Daratumumab to Bortezomib, Lenalidomide, and Dexamethasone Therapy for Transplant-Eligible Patients With Newly Diagnosed MM

Findings from a Phase 3 Trial

According to a phase 3 trial published in The New England Journal of Medicine, adding daratumumab, a monoclonal antibody targeting CD38, to bortezomib, lenalidomide, and dexamethasone (VRd) induction and consolidation therapy, as well as to lenalidomide maintenance therapy, yielded beneficial outcomes among transplantation-eligible patients with newly diagnosed multiple myeloma (MM). 

Pieter Sonneveld, MD, PhD, Erasmus MC Cancer Institute, Rotterdam, Netherlands, and coauthors aimed to assess progression-free survival as the primary end point, as well as complete response or better and minimal residual disease (MRD)-negative status as secondary end points among this patient population.

A total of 709 transplantation-eligible patients with newly diagnosed MM were enrolled in this trial and randomly assigned to 1 of 2 groups. The first group consisted of patients who received subcutaneous daratumumab and VRd induction and consolidation therapy with lenalidomide maintenance therapy (D-VRd group). The second group was made up of patients who received VRd induction and consolidation therapy with lenalidomide maintenance therapy alone (VRd group). 

Study results demonstrated that the risk of disease progression or death was lower in the D-VRd group than in the VRd group at a median follow-up of 47.5 months. The estimated percentage of patients with progression-free survival at 48 months was 84.3% in the D-VRd group versus 67.7% in the VRd group, respectively. 

In terms of secondary end points, the percentage of patients who had reached a complete response or better was 87.9% in the D-VRd group, compared with 70.1% in the VRd group. Similar trends were shown regarding the MRD-negative status end point, with 75.2% of patients in the D-VRd group reaching MRD-negative status versus 47.5% of patients in the VRd group. 

Regarding safety, 34 patients in the D-VRd group died compared to 44 patients in the VRd group. The majority of patients in both groups experienced grade 3 or 4 adverse events, the most prevalent being neutropenia and thrombocytopenia. A total of 57% of the D-VRd group experienced serious adverse events, compared with 49.3% of the VRd group. 

Based on these findings, Sonneveld and the study authors concluded, “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.”

Source: 

Sonneveld P, Dimopoulos MA, Boccadoro M, et al. Daratumumab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. New Engl J Med. Published online: January 25, 2024. doi: 10.1056/NEJMoa2312054