Mycophenolate Mofetil for Steroid-Refractory Immune-Related Hepatitis and Sclerosing Cholangitis Following Neoadjuvant Chemoimmunotherapy in Non-Small Cell Lung Cancer: A Case Report.

Introduction: Neoadjuvant chemoimmunotherapy is increasingly regarded as the standard treatment for resectable non-small cell lung cancer. Although it improves survival outcomes, immune-related adverse events can delay or prevent curative surgery. Optimal strategies for managing these adverse events in the preoperative setting remain unclear. This case is notable for being, to the best of our knowledge, the first to report curative surgery following treatment of neoadjuvant chemoimmunotherapy-induced, steroid-refractory immune-related hepatitis using mycophenolate mofetil.

Case presentation: A 74-year-old man with stage IIIA (cT2bN2M0) squamous cell carcinoma of the right lower lobe received neoadjuvant chemoimmunotherapy consisting of carboplatin, paclitaxel, and nivolumab. Following 2 treatment cycles, he developed fever, jaundice, and grade 3 liver dysfunction. Laboratory and imaging studies revealed features consistent with hepatitis and sclerosing cholangitis, suspected to be immune-related. High-dose corticosteroids were administered, resulting in only transient improvement. Owing to steroid-refractory disease, mycophenolate mofetil was initiated, leading to normalization of liver function and resolution of symptoms. However, the primary tumor exhibited regrowth following immunosuppression. Surgical resection was performed, consisting of right middle and lower lobectomy with lymph node dissection. Histopathology confirmed ypT1cN0M0 stage IA3 with 50% residual viable tumor. The postoperative course was complicated by persistent air leakage, empyema, and a bronchial fistula, ultimately requiring open-window thoracostomy. The patient was discharged and remains free of disease recurrence at follow-up.

Conclusions: This case highlights the potential role of mycophenolate mofetil in managing steroid-refractory immune-related liver injury induced by neoadjuvant chemoimmunotherapy in non-small cell lung cancer. Although immunosuppressive therapy may enable definitive surgery, it may also contribute to tumor regrowth and serious postoperative complications. As the use of neoadjuvant chemoimmunotherapy expands, further clinical experience is needed to guide the management of immune-related adverse events and ensure safe and effective surgical outcomes.