Daratumumab-based quadruplet therapy versus triplet consolidated therapy for the treatment of transplantation-eligible patients with multiple myeloma: a meta-analysis of randomized controlled trials

Keywords

multiple myeloma - daratumumab - transplantation-eligible

Introduction: Triple therapy based on a proteasome inhibitor, immunomodulator, and dexamethasone is the standard treatment for newly diagnosed patients with multiple myeloma who are candidates for autologous stem cell transplantation. However, the addition of daratumumab, an anti-CD38 monoclonal antibody, to this therapy suggests lasting benefits for this population.

Objectives: This study aims to evaluate the efficacy and safety of the addition of daratumumab to the consolidated triple therapy (bortezomib, dexamethasone, and lenalidomide/thalidomide) in patients with multiple myeloma eligible for transplantation.

Methods: Studies comparing the use of daratumumab-based quadruplet therapy versus triplet consolidated therapy in transplantation-eligible patients with multiple myeloma were searched in PubMed, Scopus, and Cochrane Central. The main outcomes were disease progression or death, complete response or better, minimal residual disease status (MRD), and neutropenia. Statistical analysis was performed using Review Manager.

Results: Three randomized controlled trials and 2081 patients were included. Daratumumab-based therapy was used to treat multiple myeloma in 1045 (50.2%) patients. Follow-up ranged from 18 to 49 months. The median age was 59.5 years, with 58% male patients. 91.5% of the patients had a 0-1 Eastern Cooperative Oncology Group (ECOG) performance status and 81.4% had standard cytogenetic risk. Disease progression or death (HR 0.44; 95% CI 0.35-0.56; p < 0.00001) was significantly lower in patients treated with the addition of daratumumab, and complete response or better (RR 2.49; 95% CI 1.63-3.81; p < 0.0001) was significantly higher in the intervention group. The occurrence of minimal residual disease also significantly favored the daratumumab group (RR 3.00; 95% CI 2.11-4.25; p < 0.00001). However, hematological adverse effects were more common among patients treated with daratumumab, such as neutropenia (RR 1.47; 95% CI 1.09-1.98; p = 0.01).

Conclusion: The addition of daratumumab to conventional triple therapy in newly diagnosed multiple myeloma patients reduces disease progression or death, increases complete response, and favors the occurrence of minimal residual disease, although it is associated with an increased risk of adverse effects such as neutropenia. Therefore, daratumumab-based therapy may be a preferred strategy to enhance treatment effectiveness.

Corresponding author: Isabela Frazão Gonçalves (e-mail: [e-mail]).

 

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No conflict of interest has been declared by the author(s).

Publication History

Article published online:
06 May 2025