Department of Medicine I (Hematology, Oncology and Stem Cell Transplantation), Medical Center, Faculty of Medicine, University of Freiburg, Hugstetter Strasse 53, D-79106, Freiburg, Germany.
Department of Internal Medicine 5 - Hematology/Oncology, University Hospital of Erlangen, Erlangen, Germany.
BMC Nephrol. 2021 Jan 18;22(1):32. doi: 10.1186/s12882-020-02226-5.
Treatment with proteasome inhibitors like carfilzomib in patients with multiple myeloma (MM) can induce thrombotic microangiopathy (TMA) characterized by neurological symptoms, acute kidney injury, hemolysis and thrombocytopenia. Successful treatment with the monoclonal antibody eculizumab was described for these patients, but reports of ideal management and definitive treatment protocols are lacking.
The first case describes a 43-years-old IgG-kappa-MM patient that developed TMA during the first course of carfilzomib-lenalidomide-dexamethasone (KRd) consolidation after autologous stem cell transplantation (ASCT). In the second case, a 59-years-old IgG-kappa-MM patient showed late-onset TMA during the fourth and last cycle of elotuzumab-KRd consolidation within the DSMM XVII study of the German study group MM (DSMM; clinicalTrials.gov Identifier: NCT03948035). Concurrently, he suffered from influenza A/B infection. Both patients had a high TMA-index for a poor prognosis of TMA. Therapeutically, in both patients plasma exchange (TPE) was initiated as soon as TMA was diagnosed. In patient #1, dialysis became necessary. For both patients, only when the complement inhibitor eculizumab was administered, kidney function and blood values impressively improved.
In this small case series, two patients with MM developed TMA due to carfilzomib treatment (CFZ-TMA), the second patient as a late-onset form. Even though TMA could have been elicited by influenza in the second patient and occurred after ASCT in both patients, with cases of TMA post-transplantation in MM being described, a relation of TMA and carfilzomib treatment was most likely. In both patients, treatment with eculizumab over two months efficiently treated TMA without recurrence and with both patients remaining responsive months after TMA onset. Taken together, we describe two cases of TMA in MM patients on carfilzomib-combination treatment, showing similar courses of this severe adverse reaction, with good responses to two months of eculizumab treatment.
在多发性骨髓瘤（MM）患者中使用蛋白酶体抑制剂（如卡非佐米）治疗可引发血栓性微血管病（TMA），其特征为神经症状、急性肾损伤、溶血性贫血和血小板减少。已成功使用单克隆抗体依库珠单抗对这些患者进行治疗，但缺乏理想管理和明确治疗方案的报告。
第一个病例描述了一名 43 岁 IgG-κ-MM 患者，在自体干细胞移植（ASCT）后，用卡非佐米-来那度胺-地塞米松（KRd）进行首次巩固治疗时发生 TMA。第二个病例是一名 59 岁 IgG-κ-MM 患者，在德国研究组 MM 的 DSMM XVII 研究中（DSMM；临床试验标识符：NCT03948035），用依鲁替尼-KRd 进行第四次也是最后一次巩固治疗时出现迟发性 TMA。同时，他患有流感 A/B 感染。两名患者的 TMA 指数均较高，预示 TMA 预后不良。治疗上，一旦诊断出 TMA，两名患者均立即开始进行血浆置换（TPE）。在患者 #1 中，需要进行透析。对于两名患者，只有当使用补体抑制剂依库珠单抗时，肾功能和血液值才会显著改善。
在本小病例系列中，两名 MM 患者因卡非佐米治疗（CFZ-TMA）发生 TMA，其中第二例为迟发性 TMA。尽管第二例患者的 TMA 可能由流感引起，而两名患者的 TMA 均发生在 ASCT 后，但已有 MM 患者移植后发生 TMA 的报道，TMA 与卡非佐米治疗之间的关系很可能存在。在这两名患者中，依库珠单抗治疗持续两个月，有效地治疗了 TMA，未再复发，且在 TMA 发病后数月内，两名患者仍对治疗有反应。综上，我们描述了两名接受卡非佐米联合治疗的 MM 患者发生 TMA 的情况，这两种严重不良反应的病程相似，对两个月的依库珠单抗治疗有良好反应。
