Background: Immune-checkpoint inhibitors (ICIs) are effective against various cancers; however, immune-related adverse events (irAEs) have been reported and the timing and risk factors are unknown. Therefore, we examined the incidence and timing of irAE occurrence. Methods: Patients who received ICIs at our hospital between 1 April 2016 and 31 March 2020 were enrolled. Patients were classified into an irAE group or non-irAE group. In addition, we examined the onset time and symptoms of irAEs for each ICI type. Results: A total of 80 patients received ICIs, of which 27 (33.8%) developed irAEs. The incidence of irAEs was 35.3% for nivolumab, 35.5% for pembrolizumab, and 28.6% for atezolizumab. The incidence of pneumonitis was 12.5%, 8.8% for dermatologic adverse events, and 6.3% for thyroid dysfunction. The earliest case of onset was after the 1st course, and the latest cases occurred after the 66th course. By the sixth course, 69% of the irAEs occurred. The positive rates for anti-thyroid peroxidase and anti-thyroglobulin antibodies were higher in the irAE group compared to the non-irAE group. Conclusions: Our findings suggest a high probability of irAEs occurring early in ICI treatment, with a diverse range of symptoms. This underscores the need for vigilant monitoring and tailored patient management during the initial courses of ICI therapy.

Background: Atezolizumab (ATZ) plus bevacizumab (BEV) combination therapy has recently been approved for the treatment of unresectable hepatocellular carcinoma. However, immune-related adverse events (irAEs), including peripheral neuropathy, have also been reported. This case report describes a multidisciplinary intervention for a patient who developed peripheral neuropathy as an irAE following ATZ+BEV combination therapy. Case presentation: The patient was a 60-year-old man with a history of hypertension. ATZ + BEV combination therapy was initiated for unresectable hepatocellular carcinoma on day 0. On day 6, he experienced a grade 2 hypertensive episode with a systolic blood pressure of 160 mmHg, despite being on amlodipine (5 mg) and azilsartan (20 mg). Based on the pharmacist’s recommendations, the amlodipine dose was increased to 10 mg. However, as hypertension persisted, an additional 20 mg of azilsartan was prescribed, ultimately stabilizing the patient’s blood pressure to approximately 110/60 mmHg. On day 23, the patient reported numbness in his extremities, which was later diagnosed as grade 3 peripheral neuropathy. Notably, data from the IMbrave150 trial indicated that the of peripheral neuropathy as an irAE was 1.5%. This prompted a consultation with a neurologist. Prednisolone (40 mg/day) was initiated on day 26, followed by steroid pulse therapy with methylprednisolone (1000 mg/day for three days) starting on day 37. Despite these interventions, the symptoms did not improve. Rehabilitation therapy was commenced on day 42 after steroid tapering. On day 48, the patient underwent a five-day course of high-dose intravenous immunoglobulin therapy, which also failed to yield improvement. Rehabilitation efforts subsequently shifted to enhancing activities of daily living. Initially, the patient required assistance to stand and faced significant difficulty walking. With consistent strength and mobility training, the patient progressed to walking with crutches and demonstrated increased walking distance. Conclusions: The pathophysiology of irAE-induced peripheral neuropathy associated with immune checkpoint inhibitors remains poorly understood. This case underscores the challenges of managing irAE-related neuropathy, which may exhibit limited responsiveness to conventional treatments. Early detection, timely intervention, and multidisciplinary approaches are crucial for optimizing patient outcomes and mitigating the impact of severe side effects.