Immunotherapy is increasingly used to treat various types of cancer; however, it can often result in immune-related adverse events (irAEs). Immune-related sclerosing cholangitis (irSC) is a rare type of hepatic irAE that has been described only in a few cases, and much remains unknown about its optimal treatment. In this report, we describe the case of a man in his 70s who was diagnosed with metastatic melanoma and treated with pembrolizumab. He experienced multiple irAEs, including irSC, which did not respond to initial prednisone treatment (2 mg/kg daily dosing). However, subsequent treatment with ursodeoxycholic acid (UDCA) resulted in complete resolution of symptoms and normalisation of laboratory and radiographic abnormalities related to irSC. Our case suggests that steroids, which are traditionally used to treat irAEs, may be ineffective for irSC and that UDCA may be a better alternative. Clinicians should be aware of this rare irAE.
Background: little is known about the incidence and characteristics of multisystem immune-related adverse events (irAEs) associated with dual-agent ipilimumab and nivolumab use. Methods: A retrospective cohort review was completed that included cancer patients seen at the Juravinski Cancer Centre who received at least one dose of ipilimumab and nivolumab from 2018 to 2022. Patient characteristics, cancer types, and irAEs were recorded. Multivariate logistic and cox regressions were completed, comparing those who developed multisystem irAEs, single irAE, and no irAE. Results: A total of 123 patients were included in this study. Out of 123 patients, 72 (59%) had melanoma, 50/123 (41%) had renal cell carcinoma (RCC), and 1/123 (1%) had breast cancer. Multisystem irAEs were seen in 40% of the overall cohort. The most common irAE type was dermatitis (22%), followed by colitis (19%) and hepatitis (17%). Conclusions: Our study demonstrated that multisystem irAEs are prevalent amongst patients receiving ipilimumab and nivolumab. It is important for both physician education and the counseling and consent of patients to monitor the potential for multiple irAEs.
Background: Immune checkpoint inhibitors (ICI) are increasingly the mainstay of oncology treatment. Immune-related adverse events (irAEs) from ICI therapy differ from cytotoxic adverse events. Cutaneous irAEs are one of the most common irAEs and require careful attention to optimize the quality of life for oncology patients. Patient and Methods: These are two cases of patients with advanced solid-tumour malignancies treated with PD-1 inhibitor therapy. Results: Both patients developed multiple pruritic hyperkeratotic lesions, which were initially diagnosed as squamous cell carcinoma from skin biopsies. The presentation as squamous cell carcinoma was atypical and, upon further pathology review, the lesions were more in keeping with a lichenoid immune reaction stemming from the immune checkpoint blockade. With the use of oral or topical steroids and immunomodulators, the lesions resolved. Conclusions: These cases emphasize that patients on PD-1 inhibitor therapy who develop lesions resembling squamous cell carcinoma on initial pathology may require an additional pathology review to assess for immune-mediated reactions, allowing appropriate immunosuppressive therapy to be initiated.
Appropriate surveillance of patients with melanoma treated with curative intent is vital to improve patient outcomes. A systematic review was conducted to capture locoregional recurrence and metastatic disease, and to evaluate the effectiveness of various surveillance strategies. MEDLINE, EMBASE, PubMed, Cochrane Database of Systematic Reviews, and National Cancer Institute Clinical Trials Database were searched. Randomized controlled trials (RCTs) and comparative studies reporting at least one patient-related outcome were included. Exclusion criteria included: published in non-English or recruited >20 % or an uncertain percentage of non-target patients without conducting a subgroup analysis for the target patients. This review was registered at PROSPERO (CRD42021246482). Among 17,978 publications from the literature search, one RCT and five non-randomized comparative studies were included and comprised 4016 patients. The aggregate evidence certainty was low for the RCT and very low for the comparative studies, as assessed by the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. For patients with stage IA-IIC melanoma, a reduced follow-up schedule with clinical follow-up strategies alone may be safe and cost-effective. For stage IIC-IIIC patients, at least two serial PET/CT or whole-body CT and brain MRI imaging within a median follow-up of 31.2 months may detect 50 % of recurrences that lead to additional management, such as surgery. PET/CT may have a higher positive predictive value and lower false positive rate compared with CT alone in detecting recurrence in stage I-III patients. Surveillance protocols should be based on individual risk of recurrence and established best practices when formulating follow-up strategies, as suggested by the studies reviewed. Future high-quality studies are needed to clarify the frequency of imaging follow-up strategies, especially in patients with high-risk stage II melanoma.