Case Report: A Case of Sintilimab-Induced Cystitis/Ureteritis and Review of Sintilimab-Related Adverse Events

Abstract

Immune checkpoint inhibitors (ICIs) have been proven to be beneficial in multiple advanced malignancies. However, the widespread use of ICIs also occurred with various immune-related adverse events (irAEs). Here, we first report a case of sintilimab-related cystitis/ureteritis. A 53-year-old man with driver gene-negative pulmonary adenocarcinoma (cT1cN3M1c, Stage IVB) was being treated with sintilimab in combination of paclitaxel-albumin and bevacizumab as second-line treatment. He was hospitalized for haematuria, pollakiuria, painful micturition and low back pain after three courses. Urinalysis showed red blood cells (RBCs) and white blood cells (WBCs) were obviously increased, and serum creatinine (sCr) level was also significantly elevated. Urine culture and cytology were both negative, and cystoscopy revealed diffused redness of bladder mucosa. Urinary ultrasonography showed mild hydronephrosis and dilated ureter. The patient was diagnosed as immunotherapy-related cystitis/ureteritis after a multidisciplinary team (MDT) meeting. Once the diagnosis was made, corticosteroid therapy was given, which rapidly resolved the patient’s symptoms and signs. Computer tomography angiography (CTA) and CT urography (CTU) was conducted after sCr level was back to normal and demonstrated ureter dilation and hydroureter. Once symptoms relieved, bladder biopsy was performed and confirmed the bladder inflammation. The patient was subsequently switched to maintenance dose of methylprednisolone and tapered gradually. Since sintilimab has been used in advanced malignancies, we first reported a rare case of sintilimab-induced cystitis/ureteritis and summarized sintilimab-related adverse events to improve the assessment and management of irAEs.

Non-bacterial Cystitis With Increased Expression of Programmed Cell Death Ligand 1 in the Urothelium: An Unusual Immune-Related Adverse Event After Atezolizumab Administration for Metastatic Breast Cancer

“…However, irAEs affecting the bladder and urinary tract are very rarely reported. Four cases of cystitis have been associated with nivolumab [ 4 - 6 ], one case with pembrolizumab [ 7 ], and one case with sintilimab [ 8 ]. In one case, combined therapy of nivolumab and ipilimumab was used [ 9 ]; in one case, cystitis occurred during nivolumab therapy and recurred during atezolizumab therapy [ 2 ].…”

Immune-related ureteritis and cystitis induced by immune checkpoint inhibitors: Case report and literature review

“…IrAEs have been suggested to occur at any time but usually develop within the first few weeks to months after administration initiation (19). In previous case reports of ICIrelated cystitis, the time from the initiation of therapy to the development of cystitis ranged from 2 to 12 months (the third to 18th cycles of ICIs) (7)(8)(9)(10)(11)(12)(13)(14)(15). In our report, the patients presented with urinary symptoms that ranged from 3 weeks to 15 weeks The timeline of the treatment course of case 3.…”

“…In previous case reports of ICI-related ureteritis/cystitis, nine cases received glucocorticoid therapy, seven cases received corticosteroids at 1.7 mg/kg/day (8)(9)(10)(11)15), two cases received glucocorticoids at 0.5 mg/kg/day (7,13), and one case received glucocorticoid pulse therapy (14). All cases acquired remission of urinary symptoms and normal urinalysis results.…”

“…We further performed a review of the literature about ICIrelated ureteritis and cystitis (7)(8)(9)(10)(11)(12)(13)(14)(15). Eight papers were retrieved to be about ICI-related cystitis and one paper about ICIrelated ureteritis/cystitis (10).…”

“…Ten cases were reported to have 11 episodes of urinary irritation after ICI therapy. Of the 10 cases, acute kidney injury was complicated in one case, and immune-related cystitis reoccurred in one case after PD-1 mAb restarting (7)(8)(9)(10)(11)(12)(13)(14)(15).…”