Horikita Fuka, Hashiguchi Junichi, Nagashima Takahiro
Department of Internal Medicine/General Medicine, Japanese Red Cross Kitami Hospital.
Rinsho Ketsueki. 2020;61(11):1611-1615. doi: 10.11406/rinketsu.61.1611.
A 69-year-old man with an unremarkable medical history presented with asymptomatic pancytopenia and diagnosed with Bence Jones protein-λ multiple myeloma (MM). Despite treatment with various chemotherapeutic regimens, myelosuppressive neutropenia occurred after each successive course; therefore, the treatment was determined to be ineffective and was discontinued. Consequently, one year after the diagnosis, a daratumumab-based therapy was initiated, and the MM was stabilized without clinical or laboratory evidences of myelosuppression. However, 18 months after the daratumumab induction, the patient developed hematochezia. Following an unremarkable lower gastrointestinal endoscopy, he presented fever and disturbed consciousness. Serum laboratory results showed liver dysfunction, and Listeria monocytogenes meningitis was diagnosed by cerebrospinal fluid examination. Empiric antibacterial treatment was administered for 3 weeks, which resolved the symptoms with no permanent neurological deficit.Daratumumab, a CD38 monoclonal antibodies, binds to expressed CD38 on myeloma cells and has an anti-myeloma cytotoxic effect but also binds to CD38 on activated macrophages. Additionally, activated macrophages play an important role in the immune defense of Listeria monocytogenes. Furthermore, inactivation of macrophages may increase the susceptibility to Listeria infection. Therefore, the possibility of infections such as Listeria meningitis should be considered in patients with MM receiving daratumumab-based therapy.
一名69岁男性，既往病史无特殊，因无症状全血细胞减少就诊，被诊断为本-周蛋白λ型多发性骨髓瘤（MM）。尽管接受了多种化疗方案治疗，但每连续一个疗程后均出现骨髓抑制性中性粒细胞减少；因此，确定治疗无效并停止。结果，诊断后一年开始使用达雷妥尤单抗治疗，MM病情稳定，无骨髓抑制的临床或实验室证据。然而，达雷妥尤单抗诱导治疗18个月后，患者出现便血。在低位胃肠内镜检查无异常后，他出现发热和意识障碍。血清实验室检查结果显示肝功能异常，脑脊液检查诊断为单核细胞增生李斯特菌脑膜炎。给予经验性抗菌治疗3周，症状缓解，无永久性神经功能缺损。达雷妥尤单抗是一种CD38单克隆抗体，可与骨髓瘤细胞上表达的CD38结合，具有抗骨髓瘤细胞毒性作用，但也可与活化巨噬细胞上的CD38结合。此外，活化巨噬细胞在单核细胞增生李斯特菌的免疫防御中起重要作用。此外，巨噬细胞失活可能增加对李斯特菌感染的易感性。因此，接受基于达雷妥尤单抗治疗的MM患者应考虑感染如李斯特菌脑膜炎的可能性。
