Proteasome inhibitors related thrombotic microangiopathy: a systematic and comprehensive review
Abstract Proteasome inhibitors (PIs) are crucial in treating multiple myeloma but carry a risk of thrombotic microangiopathy (TMA), especially with carfilzomib use. This systematic review includes 44 studies with 115 cases of PI-induced TMA, where carfilzomib was implicated in 101 cases. Treatment a...
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| Language: | English |
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Nature Publishing Group
2024-11-01
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| Series: | Blood Cancer Journal |
| Online Access: | https://doi.org/10.1038/s41408-024-01182-9 |
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| author | Can Chen Yiwei Li Pengfei Shi Shenxian Qian |
| author_facet | Can Chen Yiwei Li Pengfei Shi Shenxian Qian |
| author_sort | Can Chen |
| collection | DOAJ |
| description | Abstract Proteasome inhibitors (PIs) are crucial in treating multiple myeloma but carry a risk of thrombotic microangiopathy (TMA), especially with carfilzomib use. This systematic review includes 44 studies with 115 cases of PI-induced TMA, where carfilzomib was implicated in 101 cases. Treatment approaches varied: 28 patients received supportive care, 43 underwent therapeutic plasma exchange (TPE), 9 were treated exclusively with eculizumab (ECU), and 13 received both TPE and ECU. Notably, eculizumab significantly improved outcomes for patients unresponsive to initial TPE, achieving complete remission in seven cases. The need for dialysis emerged as a significant predictor of outcomes, often indicating a poor prognosis. For patients suspected of having PI-TMA, it is advisable to discontinue the offending medication promptly, even without definitive laboratory confirmation. In cases where diagnosis is challenging, kidney biopsy may assist if conditions permit. Comprehensive evaluation of the complement system, including genetic mutations, function, and associated complement inhibitory factor antibodies, should be included in the assessment of PI-TMA. Early administration of eculizumab may be beneficial in cases of suspected complement abnormalities or suboptimal response to initial treatments. |
| format | Article |
| id | doaj-art-7b29d318d0d747cb9830de5286caa31d |
| institution | DOAJ |
| issn | 2044-5385 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Blood Cancer Journal |
| spelling | doaj-art-7b29d318d0d747cb9830de5286caa31d2025-08-20T02:50:00ZengNature Publishing GroupBlood Cancer Journal2044-53852024-11-011411910.1038/s41408-024-01182-9Proteasome inhibitors related thrombotic microangiopathy: a systematic and comprehensive reviewCan Chen0Yiwei Li1Pengfei Shi2Shenxian Qian3Department of Hematology, Affiliated Hangzhou First People’s Hospital, Westlake University, School of MedicineDepartment of Hematology, Affiliated Hangzhou First People’s Hospital, Westlake University, School of MedicineDepartment of Hematology, Affiliated Hangzhou First People’s Hospital, Westlake University, School of MedicineDepartment of Hematology, Affiliated Hangzhou First People’s Hospital, Westlake University, School of MedicineAbstract Proteasome inhibitors (PIs) are crucial in treating multiple myeloma but carry a risk of thrombotic microangiopathy (TMA), especially with carfilzomib use. This systematic review includes 44 studies with 115 cases of PI-induced TMA, where carfilzomib was implicated in 101 cases. Treatment approaches varied: 28 patients received supportive care, 43 underwent therapeutic plasma exchange (TPE), 9 were treated exclusively with eculizumab (ECU), and 13 received both TPE and ECU. Notably, eculizumab significantly improved outcomes for patients unresponsive to initial TPE, achieving complete remission in seven cases. The need for dialysis emerged as a significant predictor of outcomes, often indicating a poor prognosis. For patients suspected of having PI-TMA, it is advisable to discontinue the offending medication promptly, even without definitive laboratory confirmation. In cases where diagnosis is challenging, kidney biopsy may assist if conditions permit. Comprehensive evaluation of the complement system, including genetic mutations, function, and associated complement inhibitory factor antibodies, should be included in the assessment of PI-TMA. Early administration of eculizumab may be beneficial in cases of suspected complement abnormalities or suboptimal response to initial treatments.https://doi.org/10.1038/s41408-024-01182-9 |
| spellingShingle | Can Chen Yiwei Li Pengfei Shi Shenxian Qian Proteasome inhibitors related thrombotic microangiopathy: a systematic and comprehensive review Blood Cancer Journal |
| title | Proteasome inhibitors related thrombotic microangiopathy: a systematic and comprehensive review |
| title_full | Proteasome inhibitors related thrombotic microangiopathy: a systematic and comprehensive review |
| title_fullStr | Proteasome inhibitors related thrombotic microangiopathy: a systematic and comprehensive review |
| title_full_unstemmed | Proteasome inhibitors related thrombotic microangiopathy: a systematic and comprehensive review |
| title_short | Proteasome inhibitors related thrombotic microangiopathy: a systematic and comprehensive review |
| title_sort | proteasome inhibitors related thrombotic microangiopathy a systematic and comprehensive review |
| url | https://doi.org/10.1038/s41408-024-01182-9 |
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