Optimal daratumumab-based regimen for patients with newly diagnosed and previously untreated multiple myeloma: systematic review and component network meta-analysis

Abstract Background Daratumumab (Dara)-based regimens have been investigated in randomized controlled trials (RCTs) involving patients with newly diagnosed and previously untreated multiple myeloma (NDMM), but the optimal daratumumab-based regimen remains unclear. This study compares the efficacy of...

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Main Authors: Xiaohua Huang, Jia Zhou, Yuxiao Qian, Jing He, Lu Yang, Zhigang Wang, Diu Wei, Mengjie Li, Wei Ma, Haiyan Lang
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Systematic Reviews
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Online Access:https://doi.org/10.1186/s13643-025-02804-4
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author Xiaohua Huang
Jia Zhou
Yuxiao Qian
Jing He
Lu Yang
Zhigang Wang
Diu Wei
Mengjie Li
Wei Ma
Haiyan Lang
author_facet Xiaohua Huang
Jia Zhou
Yuxiao Qian
Jing He
Lu Yang
Zhigang Wang
Diu Wei
Mengjie Li
Wei Ma
Haiyan Lang
author_sort Xiaohua Huang
collection DOAJ
description Abstract Background Daratumumab (Dara)-based regimens have been investigated in randomized controlled trials (RCTs) involving patients with newly diagnosed and previously untreated multiple myeloma (NDMM), but the optimal daratumumab-based regimen remains unclear. This study compares the efficacy of daratumumab-containing regimens for NDMM patients and explores optimal combinations. Methods Databases were searched from inception until February 29, 2024. Trials comparing regimens with and without daratumumab, as well as their mutual comparisons, were included. Random effects models for serious adverse events (SAEs) and fixed effects models for other outcomes were utilized in both network meta-analysis (NMA) and component NMA (CNMA), with pooled effects estimated. The efficacy of all possible combinations of daratumumab with other drugs was assessed. Results A total of 17 trials were included, enrolling 7261 patients, of whom 2083 were treated with daratumumab. The optimal regimens for different outcomes were identified as follows: Dara-bortezomib (V)-melphalan (M)-corticosteroids (D) (Dara-VMD) showed the best results for both overall response rate (ORR) [RR = 1.97; 95% CI: 1.42 to 2.75; I 2 = 0.00%; 16 trials; 7136 participants; P = 0.00] and ≥ very good partial response (≥ VGPR) [RR = 7.46; 95% CI: 4.10 to 13.46; I 2 = 23.96%; 16 trials; 7118 participants; P = 0.00]; Dara-V-thalidomide (T)-D (Dara-VTD) was optimal for achieving ≥ complete response (≥ CR) [RR = 14.15; 95% CI: 3.74 to 53.52; I 2 = 0.00%; 17 trials; 7261 participants; P = 0.00]. The individual effects of daratumumab were calculated as follows: [ORR: RR = 1.14; 95% CI: 1.08 to 1.21; I 2 = 0.00%; 16 trials; 7136 participants; P = 0.00; ≥ VGPR: RR = 1.46; 95% CI: 1.36 to 1.58; I 2 = 23.96%; 16 trials; 7118 participants; P = 0.00; ≥ CR: RR = 1.77; 95% CI: 1.55 to 1.99; I 2 = 0.00; 17 trials; 7261 participants; P = 0.00; progression-free survival (PFS): hazard ratio (HR) = 0.53; 95% CI: 0.43 to 0.65; I 2 = 0.00%; 13 trials; 5977 participants; P = 0.00; overall survival (OS): HR = 0.68; 95% CI: 0.58 to 0.79; I 2 = 28.97%; 12 trials; 5977 participants; P = 0.00]. Additionally, the optimal regimens for PFS and OS were Dara-lenalidomide (R)-D [HR = 0.37; 95% CI: 0.23 to 0.61; I 2 = 0.00%; 13 trials; 5977 participants; P = 0.00] and Dara-VRD [HR = 0.40; 95% CI: 0.19 to 0.85; I 2 = 28.97%; 12 trials; 5977 participants; P = 0.02], respectively. Finally, CNMA indicated that Dara-VRD, Dara-carfilzomib (K)-RD, Dara-RD, and Dara-cyclophosphamide (C)-RD were four regimens, which could improve remission rate, and reduce death or progression during induction and prolong lifetime. Conclusions Dara-VRD, Dara-KRD, Dara-RD, and Dara-CRD are optimal daratumumab-based regimens for patients with newly diagnosed and previously untreated multiple myeloma.
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spelling doaj-art-86c41ba1407e4f99804f2cccc9fcaf062025-08-20T02:32:08ZengBMCSystematic Reviews2046-40532025-05-0114111310.1186/s13643-025-02804-4Optimal daratumumab-based regimen for patients with newly diagnosed and previously untreated multiple myeloma: systematic review and component network meta-analysisXiaohua Huang0Jia Zhou1Yuxiao Qian2Jing He3Lu Yang4Zhigang Wang5Diu Wei6Mengjie Li7Wei Ma8Haiyan Lang9Haematology Department, Dongzhimen Hospital, Beijing University of Chinese MedicineThe First Clinical Medical College, Guangzhou University of Chinese MedicineThe First Clinical Medicine College, Beijing University of Chinese MedicineHaematology Department, The First Affiliated Hospital of Guangzhou University of Traditional Chinese MedicineHaematology Department, Dongzhimen Hospital, Beijing University of Chinese MedicineHaematology Department, Dongzhimen Hospital, Beijing University of Chinese MedicineHaematology Department, Dongzhimen Hospital, Beijing University of Chinese MedicineHaematology Department, Dongzhimen Hospital, Beijing University of Chinese MedicineHaematology Department, Dongzhimen Hospital, Beijing University of Chinese MedicineHaematology Department, Dongzhimen Hospital, Beijing University of Chinese MedicineAbstract Background Daratumumab (Dara)-based regimens have been investigated in randomized controlled trials (RCTs) involving patients with newly diagnosed and previously untreated multiple myeloma (NDMM), but the optimal daratumumab-based regimen remains unclear. This study compares the efficacy of daratumumab-containing regimens for NDMM patients and explores optimal combinations. Methods Databases were searched from inception until February 29, 2024. Trials comparing regimens with and without daratumumab, as well as their mutual comparisons, were included. Random effects models for serious adverse events (SAEs) and fixed effects models for other outcomes were utilized in both network meta-analysis (NMA) and component NMA (CNMA), with pooled effects estimated. The efficacy of all possible combinations of daratumumab with other drugs was assessed. Results A total of 17 trials were included, enrolling 7261 patients, of whom 2083 were treated with daratumumab. The optimal regimens for different outcomes were identified as follows: Dara-bortezomib (V)-melphalan (M)-corticosteroids (D) (Dara-VMD) showed the best results for both overall response rate (ORR) [RR = 1.97; 95% CI: 1.42 to 2.75; I 2 = 0.00%; 16 trials; 7136 participants; P = 0.00] and ≥ very good partial response (≥ VGPR) [RR = 7.46; 95% CI: 4.10 to 13.46; I 2 = 23.96%; 16 trials; 7118 participants; P = 0.00]; Dara-V-thalidomide (T)-D (Dara-VTD) was optimal for achieving ≥ complete response (≥ CR) [RR = 14.15; 95% CI: 3.74 to 53.52; I 2 = 0.00%; 17 trials; 7261 participants; P = 0.00]. The individual effects of daratumumab were calculated as follows: [ORR: RR = 1.14; 95% CI: 1.08 to 1.21; I 2 = 0.00%; 16 trials; 7136 participants; P = 0.00; ≥ VGPR: RR = 1.46; 95% CI: 1.36 to 1.58; I 2 = 23.96%; 16 trials; 7118 participants; P = 0.00; ≥ CR: RR = 1.77; 95% CI: 1.55 to 1.99; I 2 = 0.00; 17 trials; 7261 participants; P = 0.00; progression-free survival (PFS): hazard ratio (HR) = 0.53; 95% CI: 0.43 to 0.65; I 2 = 0.00%; 13 trials; 5977 participants; P = 0.00; overall survival (OS): HR = 0.68; 95% CI: 0.58 to 0.79; I 2 = 28.97%; 12 trials; 5977 participants; P = 0.00]. Additionally, the optimal regimens for PFS and OS were Dara-lenalidomide (R)-D [HR = 0.37; 95% CI: 0.23 to 0.61; I 2 = 0.00%; 13 trials; 5977 participants; P = 0.00] and Dara-VRD [HR = 0.40; 95% CI: 0.19 to 0.85; I 2 = 28.97%; 12 trials; 5977 participants; P = 0.02], respectively. Finally, CNMA indicated that Dara-VRD, Dara-carfilzomib (K)-RD, Dara-RD, and Dara-cyclophosphamide (C)-RD were four regimens, which could improve remission rate, and reduce death or progression during induction and prolong lifetime. Conclusions Dara-VRD, Dara-KRD, Dara-RD, and Dara-CRD are optimal daratumumab-based regimens for patients with newly diagnosed and previously untreated multiple myeloma.https://doi.org/10.1186/s13643-025-02804-4DaratumumabNewly diagnosedMultiple myelomaLenalidomideComponent network meta-analysis
spellingShingle Xiaohua Huang
Jia Zhou
Yuxiao Qian
Jing He
Lu Yang
Zhigang Wang
Diu Wei
Mengjie Li
Wei Ma
Haiyan Lang
Optimal daratumumab-based regimen for patients with newly diagnosed and previously untreated multiple myeloma: systematic review and component network meta-analysis
Systematic Reviews
Daratumumab
Newly diagnosed
Multiple myeloma
Lenalidomide
Component network meta-analysis
title Optimal daratumumab-based regimen for patients with newly diagnosed and previously untreated multiple myeloma: systematic review and component network meta-analysis
title_full Optimal daratumumab-based regimen for patients with newly diagnosed and previously untreated multiple myeloma: systematic review and component network meta-analysis
title_fullStr Optimal daratumumab-based regimen for patients with newly diagnosed and previously untreated multiple myeloma: systematic review and component network meta-analysis
title_full_unstemmed Optimal daratumumab-based regimen for patients with newly diagnosed and previously untreated multiple myeloma: systematic review and component network meta-analysis
title_short Optimal daratumumab-based regimen for patients with newly diagnosed and previously untreated multiple myeloma: systematic review and component network meta-analysis
title_sort optimal daratumumab based regimen for patients with newly diagnosed and previously untreated multiple myeloma systematic review and component network meta analysis
topic Daratumumab
Newly diagnosed
Multiple myeloma
Lenalidomide
Component network meta-analysis
url https://doi.org/10.1186/s13643-025-02804-4
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