Efficacy and safety of daratumumab-based quadruplet therapy vs non-daratumumab-based triplet therapy in newly diagnosed multiple myeloma patients: A GRADE assessed systematic review and meta-analysis of randomized controlled trials
In brief
Adding daratumumab halves progression risk and doubles MRD negativity in new myeloma
In a meta-analysis of seven randomized trials involving 3,443 newly diagnosed multiple myeloma patients, daratumumab-based quadruplet therapy cut the risk of progression or death by about 50% and achieved minimal residual disease negativity roughly twice as often as standard triplet regimens. Benefits appeared in both standard- and high-risk cytogenetic groups, but neutropenia, thrombocytopenia and infections were more frequent, requiring clinicians to balance stronger disease control against higher toxicity.
- Journal
- Therapeutic advances in hematology (Q1)
- Published
- 11 September 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Muhammad Osama, Muhammad Haris Khan, Ammara Tahir, Amna Hussain, Ahmad Iftikhar, Aizaz Ali, et al.
- PMID
- 42732301
- DOI
- 10.1177/20406207261489040
Why clinicians should know about it
- Picked for Transplantation (top studies of the week, 20 September 2026): Multiple myeloma therapy review, unrelated to transplantation
- Picked for Hematology (top studies of the week, 20 September 2026): GRADE‑assessed meta‑analysis of daratumumab quadruplet vs triplet in NDMM
Abstract
BACKGROUND: Multiple myeloma (MM) is the second most common hematologic malignancy worldwide. Recent therapeutic innovations, including the addition of daratumumab to standard regimens, have shown promising improvements in patient outcomes. OBJECTIVES: This study aims to compare the efficacy and safety of daratumumab-based quadruplet therapy regimens with standard triplet therapy regimens in newly diagnosed multiple myeloma (NDMM) patients. DESIGN: Systematic review and meta-analysis of randomized controlled trials. DATA SOURCES AND METHODS: A comprehensive literature search was conducted on PubMed, Cochrane Library, Embase, and ClinicalTrials.gov from inception to April 2026. Primary outcomes were Progression-free survival (PFS) and Minimal residual disease (MRD) negativity. Subgroup analysis based on cytogenetic risk was performed. The statistical assessment was done using The Review Manager (RevMan, Version 5.4). RESULTS: Our meta-analysis included 7 RCTs, comprising 3 studies in transplant-eligible multiple myeloma (TE-MM) and 4 in transplant-ineligible multiple myeloma (TIE-MM) patients, containing 3,443 patients (1,759 in the daratumumab group and 1684 in the non-daratumumab group). The median age across studies ranged from approximately 59 to 76 years. Daratumumab-based therapy demonstrated significantly higher PFS (HR 0.50, 95%CI: 0.43- 0.58, p < 0.00001). The analysis showed statistically significant high MRD negativity with daratumumab based quadruplet therapy compared to non-Dara triplet arm (RR 1.99, 95%CI 1.59-2.50, P<0.00001). Subgroup analysis based on cytogenetic risk demonstrated significant improved PFS in standard-risk (HR 0.45) as well as high-risk (HR 0.67), whereas MRD negativity increased significantly only in standard-risk (RR 1.76) but not high-risk (RR 1.23). Daratumumab-based quadruplet therapy was associated with increased neutropenia (56.2% vs 40.3%), thrombocytopenia (40.7% vs 32.5%), and infections (33.1% vs 23.3%). CONCLUSION: The meta-analysis shows higher efficacy yet higher adverse events in Daratumumab-based quadruplet therapy for NDMM patients (TE, and TIE).
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.