Two cases of nonbacterial cystitis associated with nivolumab, the anti-programmed-death-receptor-1 inhibitor

Shimatani, Kimihiro; Yoshimoto, T; Doi, Yutaka; Sonoda, Takashi; Yamamoto, Shingo; Kanematsu, Akihiro

doi:10.1016/j.eucr.2017.12.006

Cited by 22 publications

(24 citation statements)

References 4 publications

(3 reference statements)

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“…Interestingly, two recent case reports highlighted non-bacterial cystitis as a potential side effect of PD-1 blockade in bladder cancer patients (32), consistent with reports of non-bacterial cystitis adverse events from other trial data. It is interesting to note that PD-1 knockout is required, but not sufficient alone, to induce a murine model of autoimmune cystitis (33).…”

Section: Discussionsupporting

confidence: 81%

PD-L2 Is Constitutively Expressed in Normal and Malignant Urothelium

et al. 2021

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The use of immune checkpoint blockade, in particular PD-1 and PD-L1 inhibitors, is now commonplace in many clinical settings including the treatment of muscle-invasive bladder cancer (MIBC). Notwithstanding, little information exists regarding the expression of the alternative PD-1 ligand, PD-L2 in urothelial bladder cancer (UBC). We therefore set out to characterise the expression of PD-L2 in comparison to PD-L1. Firstly, we assessed PD-L2 expression by immunohistochemistry and found widespread expression of PD-L2 in UBC, albeit with reduced expression in MIBC. We further investigated these findings using RNA-seq data from a cohort of 575 patients demonstrating that PDCD1LG2 (PD-L2) is widely expressed in UBC and correlated with CD274 (PD-L1). However, in contrast to our immunohistochemistry findings, expression was significantly increased in advanced disease. We have also provided detailed evidence of constitutive PD-L2 expression in normal urothelium and propose a mechanism by which PD-L2 is cleaved from the cell surface in MIBC. These data provide a comprehensive assessment of PD-L2 in UBC, showing PD-L2 is abundant in UBC and, importantly, constitutively present in normal urothelium. These data have implications for future development of immune checkpoint blockade, and also the understanding of the function of the immune system in the normal urinary bladder.

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Section: Discussionsupporting

confidence: 81%

PD-L2 Is Constitutively Expressed in Normal and Malignant Urothelium

et al. 2021

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“…ICI-induced cystitis is extremely rare, with only three cases reported in the literature so far (Table 1). 5,6 In the clinical setting, a complaint of dysuria from a patient on ICI therapy should be considered a diagnostic clue for irAE cystitis. This is the first report of expression of PD-L1 in the urothelial epithelium in a patient with irAE cystitis.…”

Section: Discussionmentioning

confidence: 99%

Non‐bacterial cystitis with increased expression of programmed death‐ligand 1 in the urothelium: An unusual immune‐related adverse event during treatment with pembrolizumab for lung adenocarcinoma

et al. 2020

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“…Common irAEs of nivolumab were reported to be fatigue (34.2%), rash (25.9%), and diarrhea (19.2%) 1 . Besides, recent reports have demonstrated that nivolumab might cause irAEs associated with the urinary tract 2,3 . Here, we report a case of cystitis as an irAE associated with nivolumab administration.…”

Section: Introductionmentioning

confidence: 73%

“…Nivolumab, which blocks the PD‐1 receptor, is increasingly being used as drug therapy for various tumors. Nivolumab is known to induce various irAEs throughout the body, and recent reports have demonstrated that nivolumab might affect also the urinary tract as irAEs, although the specific incidence remains unknown 2,3 …”

Section: Discussionmentioning

confidence: 99%

Improvement of urinary symptoms after bladder biopsy: A case of pathologically proven allergy‐related cystitis during administration of nivolumab

et al. 2021

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Introduction We present a case of cystitis, which was considered to be an immune‐related adverse event associated with nivolumab administration. Case presentation A 47‐year‐old man suffered from sudden onset urinary symptoms after 18 cycles of nivolumab treatment for stage IV pulmonary adenocarcinoma. Urine culture and urine cytology were both negative. The symptoms were inferred to be related to nivolumab administration, and a bladder biopsy under spinal anesthesia was performed. The histopathological examination showed the evidence of allergic‐related cystitis. We planned to administer corticosteroids, but the urinary symptoms disappeared after the bladder biopsy. Nivolumab treatment was continued without recurrent bladder symptoms. Conclusion We reported a case of cystitis after treatment with nivolumab, which served as a reminder to consider the possibility of immune‐related adverse events as a potential cause for any symptoms that develop during treatment with immuno‐oncology drugs.

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Two cases of nonbacterial cystitis associated with nivolumab, the anti-programmed-death-receptor-1 inhibitor

Cited by 22 publications

References 4 publications

PD-L2 Is Constitutively Expressed in Normal and Malignant Urothelium

PD-L2 Is Constitutively Expressed in Normal and Malignant Urothelium

Non‐bacterial cystitis with increased expression of programmed death‐ligand 1 in the urothelium: An unusual immune‐related adverse event during treatment with pembrolizumab for lung adenocarcinoma

Improvement of urinary symptoms after bladder biopsy: A case of pathologically proven allergy‐related cystitis during administration of nivolumab

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