Daratumumab followed by tocilizumab for treatment of late antibody-mediated rejection in renal transplant recipients with high or moderate levels of de novo donor-specific antibodies: a pilot study
Abstract Background Effective treatment of late antibody-mediated rejection (late AMR) is still an unmet medical need. Clearing donor-specific antibody (DSA) and preventing its rebound is the ideal goal of treatment. Methods We have summarized the clinical data from seven patients with late or chron...
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2025-01-01
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| Online Access: | https://doi.org/10.1186/s12882-025-03951-5 |
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| author | Zhiliang Guo Rula Sa Daqiang Zhao Songxia Li Hui Guo Lan Zhu Gang Chen |
| author_facet | Zhiliang Guo Rula Sa Daqiang Zhao Songxia Li Hui Guo Lan Zhu Gang Chen |
| author_sort | Zhiliang Guo |
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| description | Abstract Background Effective treatment of late antibody-mediated rejection (late AMR) is still an unmet medical need. Clearing donor-specific antibody (DSA) and preventing its rebound is the ideal goal of treatment. Methods We have summarized the clinical data from seven patients with late or chronic active AMR after renal transplantation who received daratumumab (Dara)-based treatment first (Phase 1) and then tocilizumab (TCZ) therapy (Phase 2). Phase 1 consisted of an intensive treatment period (Dara plus PP/IVIG) and a maintenance treatment period (Dara alone). The main clinical indicators were DSA, Banff scores and renal function. Results After 4 to 17 weeks of intensive treatment, the MFI values of DSA in five of the seven patients fell below 5,000. During Dara maintenance treatment, only one patient’s DSA became negative, and the remaining six patients’ DSAs remained relatively stable or showed rebound. However, after TCZ treatment was begun, the DSA eventually became negative in three patients and decreased to low levels (< 3,500) in the other three patients. Also, our treatment stabilized renal function in all patients. At 24–28 months after treatment, renal biopsy showed partial remission of microvascular inflammation in four of six patients. In addition, capillary C4d deposition became negative in all patients (P = 0.001), and the mean score of i-IFTA was significantly reduced (P = 0.012). Other chronic injury scores did not change significantly. Conclusions This new therapy combining Dara and TCZ achieved a good desensitization effect, providing an important reference point for designing better-optimized treatment of late or chronic active AMR in the future. Trial registration This retrospectively study was approved by the Ethics Committee of Tongji Hospital, Wuhan, China (TJ-IRB20230729). |
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| language | English |
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| publisher | BMC |
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| series | BMC Nephrology |
| spelling | doaj-art-106243886823490ca8bd5a3ada5f288e2025-01-12T12:11:36ZengBMCBMC Nephrology1471-23692025-01-0126111110.1186/s12882-025-03951-5Daratumumab followed by tocilizumab for treatment of late antibody-mediated rejection in renal transplant recipients with high or moderate levels of de novo donor-specific antibodies: a pilot studyZhiliang Guo0Rula Sa1Daqiang Zhao2Songxia Li3Hui Guo4Lan Zhu5Gang Chen6Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Key Laboratory of Organ Transplantation, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Huazhong University of Science and Technology, Ministry of Education, Chinese Academy of Medical SciencesInstitute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Key Laboratory of Organ Transplantation, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Huazhong University of Science and Technology, Ministry of Education, Chinese Academy of Medical SciencesInstitute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Key Laboratory of Organ Transplantation, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Huazhong University of Science and Technology, Ministry of Education, Chinese Academy of Medical SciencesInstitute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Key Laboratory of Organ Transplantation, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Huazhong University of Science and Technology, Ministry of Education, Chinese Academy of Medical SciencesInstitute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Key Laboratory of Organ Transplantation, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Huazhong University of Science and Technology, Ministry of Education, Chinese Academy of Medical SciencesInstitute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Key Laboratory of Organ Transplantation, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Huazhong University of Science and Technology, Ministry of Education, Chinese Academy of Medical SciencesInstitute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Key Laboratory of Organ Transplantation, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Huazhong University of Science and Technology, Ministry of Education, Chinese Academy of Medical SciencesAbstract Background Effective treatment of late antibody-mediated rejection (late AMR) is still an unmet medical need. Clearing donor-specific antibody (DSA) and preventing its rebound is the ideal goal of treatment. Methods We have summarized the clinical data from seven patients with late or chronic active AMR after renal transplantation who received daratumumab (Dara)-based treatment first (Phase 1) and then tocilizumab (TCZ) therapy (Phase 2). Phase 1 consisted of an intensive treatment period (Dara plus PP/IVIG) and a maintenance treatment period (Dara alone). The main clinical indicators were DSA, Banff scores and renal function. Results After 4 to 17 weeks of intensive treatment, the MFI values of DSA in five of the seven patients fell below 5,000. During Dara maintenance treatment, only one patient’s DSA became negative, and the remaining six patients’ DSAs remained relatively stable or showed rebound. However, after TCZ treatment was begun, the DSA eventually became negative in three patients and decreased to low levels (< 3,500) in the other three patients. Also, our treatment stabilized renal function in all patients. At 24–28 months after treatment, renal biopsy showed partial remission of microvascular inflammation in four of six patients. In addition, capillary C4d deposition became negative in all patients (P = 0.001), and the mean score of i-IFTA was significantly reduced (P = 0.012). Other chronic injury scores did not change significantly. Conclusions This new therapy combining Dara and TCZ achieved a good desensitization effect, providing an important reference point for designing better-optimized treatment of late or chronic active AMR in the future. Trial registration This retrospectively study was approved by the Ethics Committee of Tongji Hospital, Wuhan, China (TJ-IRB20230729).https://doi.org/10.1186/s12882-025-03951-5Antibody-mediated rejectionDonor-specific antibodyDaratumumabKidney transplantationTocilizumab |
| spellingShingle | Zhiliang Guo Rula Sa Daqiang Zhao Songxia Li Hui Guo Lan Zhu Gang Chen Daratumumab followed by tocilizumab for treatment of late antibody-mediated rejection in renal transplant recipients with high or moderate levels of de novo donor-specific antibodies: a pilot study BMC Nephrology Antibody-mediated rejection Donor-specific antibody Daratumumab Kidney transplantation Tocilizumab |
| title | Daratumumab followed by tocilizumab for treatment of late antibody-mediated rejection in renal transplant recipients with high or moderate levels of de novo donor-specific antibodies: a pilot study |
| title_full | Daratumumab followed by tocilizumab for treatment of late antibody-mediated rejection in renal transplant recipients with high or moderate levels of de novo donor-specific antibodies: a pilot study |
| title_fullStr | Daratumumab followed by tocilizumab for treatment of late antibody-mediated rejection in renal transplant recipients with high or moderate levels of de novo donor-specific antibodies: a pilot study |
| title_full_unstemmed | Daratumumab followed by tocilizumab for treatment of late antibody-mediated rejection in renal transplant recipients with high or moderate levels of de novo donor-specific antibodies: a pilot study |
| title_short | Daratumumab followed by tocilizumab for treatment of late antibody-mediated rejection in renal transplant recipients with high or moderate levels of de novo donor-specific antibodies: a pilot study |
| title_sort | daratumumab followed by tocilizumab for treatment of late antibody mediated rejection in renal transplant recipients with high or moderate levels of de novo donor specific antibodies a pilot study |
| topic | Antibody-mediated rejection Donor-specific antibody Daratumumab Kidney transplantation Tocilizumab |
| url | https://doi.org/10.1186/s12882-025-03951-5 |
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