Impact of Daratumumab in Transplant Eligible/Ineligible Patients with Newly Diagnosed Multiple Myeloma: An Updated Meta-Analysis of Phase- III Trials

Background and Objectives: Daratumumab, a monoclonal antibody against CD38, has shown promising results in multiple myeloma (MM). We aimed to analyze its efficacy in newly diagnosed patients with MM. Materials and Methods: A search was conducted in PubMed, Cochrane, and Clinicaltrials.gov using the MeSH terms “daratumumab” or “Darzalex” and “multiple myeloma” covering the period until 2024. The Mantel-Haenzel formula was used to calculate the pooled risk ratio (RR), and the Generic Inverse Variance method was used to determine the pooled hazard ratio for disease progression, using RevMan version 5.4 at 95% confidence interval (CI). A P value of less than 0.05 was significant. Results: A total of 6 phase-III RCTs were analyzed. The use of daratumumab was associated with 39% fewer events of progression of disease or deaths in the TE group (RR= 0.61; 95% CI= 0.39 to 0.93; p=0.02) and 29% lower in the TIE group (RR= 0.71; 95% CI= 0.53 to 0.94; p=0.02). The hazard ratio for progression or death with daratumumab group versus control in both transplant eligible (TE) (HR= 0.44; 95% CI= 0.35 to 0.57; p<0.00001) or transplant ineligible (TIE) (HR= 0.47; 95% CI= 0.38 to 0.59; p<0.00001) group was significantly lower. Daratumumab significantly increased overall response rate (ORR) (RR= 1.20; 95% CI= 1.11 to 1.30 ; p<0.00001) and complete response (CR) (RR= 1.34; 95% CI= 1.02 to 1.76; p=0.04) in the TIE group only. Conclusions: Daratumumab showed benefits in both TE and TIE patients with newly diagnosed multiple myeloma. It significantly reduced the risk of disease progression or death and improved clinical outcomes regarding ORR and CR, suggesting an effective treatment option in these patient groups.