Original message:
In this phase III trial, the efficacy of daratumumab, bortezomib, lenalidomide, and dexamethasone (D-VRD) was compared with VRD alone in transplant-eligible multiple myeloma patients. After a median follow-up of approximately 4 years, the combination of daratumumab demonstrated improved progression-free survival, higher complete response rates, and greater minimal residual disease negativity. The most prevalent grade 3 or 4 adverse events included neutropenia (62.1% in the D-VRD group vs 51.0% in the VRD group), thrombocytopenia (29.1% vs 17.3%), diarrhea (10.5% vs 7.8%). , pneumonia (10.5% vs. 6.1%), and febrile neutropenia (9.4% vs. 10.1%). Grade 3 or 4 peripheral neuropathy occurred in 6.0% of D-VRD patients and 4.9% of VRD patients.
The addition of subcutaneous daratumumab to VRD induction and consolidation therapy with lenalidomide maintenance therapy demonstrated significant clinical benefit with a favorable benefit-risk profile in transplant-eligible patients with newly diagnosed multiple myeloma.
Summary:
background
Daratumumab, a monoclonal antibody that targets CD38, has been approved for use with standard myeloma regimens. Evaluation of subcutaneous daratumumab combined with bortezomib, lenalidomide, and dexamethasone (VRD) is needed for the treatment of transplant-eligible patients with newly diagnosed multiple myeloma.
Method
In this phase 3 trial, we randomized 709 transplant-eligible patients with newly diagnosed multiple myeloma to receive subcutaneous daratumumab combined with VRD induction and consolidation therapy and lenalidomide maintenance therapy (D-VRD group) or induction and consolidation therapy alone. Assigned randomly. VRD and maintenance therapy with lenalidomide alone (VRD group). The primary endpoint was progression-free survival. The main secondary endpoints were complete response or improvement and negative minimal residual disease (MRD) status.
Result
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; confidence interval 95%, 0.30 to 0.59; P ) <0.001); The P value exceeded the predefined stopping threshold (P=0.0126). The percentage of patients with a complete response or better response 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 negative MRD status (75.2% vs. 47.5%). %, p<0.001). There were 34 deaths in the D-VRD group and 44 deaths in the VRD group. Grade 3 or 4 adverse events occurred in the majority of 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 patients in the D-VRD group and 49.3% of patients in the VRD group.
conclusion
The addition of subcutaneous daratumumab to VRD induction and consolidation therapy as well as lenalidomide maintenance therapy provided significant benefit in terms of progression-free survival in transplant-eligible patients with newly diagnosed multiple myeloma.