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

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.