Destructive Mono-Arthritis Caused by Mycobacterium bovis during Treatment with Pembrolizumab in a Patient Previously Treated with BCG Instillations for Bladder Cancer: A Case Report

E. Cynthia, Huijts Susanne M, Lubbe Peter AHM van der, Robbrecht Debbie G.J.
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Abstract

Immune checkpoint inhibitor (ICI) treatment is an integral part of second line treatment of patients with urothelial carcinoma (UC) as well as in first line in cisplatin-ineligible patients with PD-L1 positive tumours. A substantial proportion of patients with bladder cancer have been treated with intravesical Mycobacterium bovis BCG in the past. Although it is rare, disseminated infections with Mycobacterium bovis have been described, but not in association with ICI treatment. We herein report a case of destructive monoarthritis caused by Mycobacterium bovis in a patient previously treated with intravesical BCG and a recent initiation of the ICI pembrolizumab in first line for metastatic UC. A culture of synovial fluid from the involved wrist was positive for Mycobacterium bovis. Based on whole genome sequencing based-subtyping, the identified Mycobacterium was shown to be related with the previous BCG instillations. Because of severe complaints and progressive destruction of the patients’ wrist, it was decided to interrupt the pembrolizumab. At that moment, following the seventh cycle of pembrolizumab, evaluation showed a partial disease response. Following systemic treatment with triple combination therapy (Isoniazid, Rifampicin, Ethambutol) and surgery, the complaints of the wrist gradually improved. This is the first report describing a disseminated Mycobacterium bovis infection in a patient treated with an ICI and previous BCG instillations for bladder cancer. This is of relevance, because an increasing number of bladder cancer patients, previously treated with BCG instillations, will be treated with an ICI in advanced disease setting.
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一例先前接受BCG灌注治疗膀胱癌症的患者在接受Pembrolizumab治疗期间由牛分枝杆菌引起的破坏性单关节炎:病例报告
免疫检查点抑制剂(ICI)治疗是尿路上皮癌(UC)患者二线治疗以及PD-L1阳性肿瘤顺铂不合格患者一线治疗的组成部分。相当一部分癌症患者过去曾接受过膀胱内牛分枝杆菌BCG治疗。虽然牛分枝杆菌的播散性感染很罕见,但与ICI治疗无关。我们在此报告了一例由牛分枝杆菌引起的破坏性单关节炎患者,该患者先前接受过膀胱内BCG治疗,最近开始在转移性UC的一线使用ICI pembrolizumab。来自受累手腕的滑膜液培养物对牛分枝杆菌呈阳性。基于全基因组测序的分型,鉴定出的分枝杆菌与以前的BCG滴注有关。由于严重的主诉和患者手腕的逐渐损伤,决定中断pembrolizumab治疗。在那一刻,pembrolizumab第七个周期后,评估显示部分疾病反应。经过三重联合治疗(异烟肼、利福平、乙胺丁醇)和手术的全身治疗,手腕的主诉逐渐改善。这是第一份报告,描述了一名接受ICI和先前BCG膀胱癌症滴注治疗的患者的牛分枝杆菌感染。这是相关的,因为越来越多的癌症患者,以前接受过BCG滴注治疗,将在晚期疾病环境中接受ICI治疗。
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