Immune-related adverse events in patients with low baseline serum IL-6 treated with durvalumab plus tremelimumab for hepatocellular carcinoma: a case series.

Systemic therapy for advanced hepatocellular carcinoma (HCC) has progressed significantly, yet the management of immune-related adverse events (irAEs) remains a challenge, particularly with anti-CTLA-4 and anti-PD-L1 antibodies. We present two cases of severe irAEs during durvalumab plus tremelimumab (DT) therapy, demonstrating successful management and favorable outcomes. In Case 1, a 76-year-old male with metabolic-associated steatotic liver disease-related HCC experienced disease progression after lenvatinib and subsequently initiated DT therapy. He developed Grade 3 immune-related myositis at week 5, which was successfully managed with prednisolone. A partial response (PR) was achieved and maintained, with a 55% tumor reduction at 8 months. In Case 2, a 73-year-old male with alcoholic cirrhosis and a 16-cm HCC received DT therapy. On day 19, he developed Grade 3 immune-related hepatitis and thyroiditis, which were controlled with prednisolone. After steroid tapering, durvalumab was successfully rechallenged, maintaining a 38% tumor reduction at 6 months with a sustained PR. In the case series, lower baseline serum interleukin (IL)-6 levels were associated with the development of Grade ≥ 3 irAEs. These findings suggest that IL-6 may serve as a predictive biomarker, aiding in risk assessment and the optimization of individualized treatment strategies prior to anti-CTLA-4 therapy.