S5891 A Strategy Utilizing Tocilizumab, Budesonide, and Mycophenolate Mofetil in the Peri-Operative Period to Achieve Biochemical Remission in High-Grade Immune Checkpoint Inhibitor-Mediated Cholangiohepatitis: A Case Study

Introduction: About one-third of patients who develop high-grade immune-mediated hepatobiliary toxicity (IMH) induced by immune checkpoint inhibitors (ICI) may exhibit steroid-refractoriness requiring escalation of treatment. Some cases with a cholestatic component of liver injury, associated with anti-PD-1 inhibitor therapy, can exhibit suboptimal response to systemic corticosteroids alone. Emerging clinical experience has shown that tocilizumab, an IL-6 receptor antagonist, is a viable adjunctive treatment option. We present a case of ICI-mediated cholangiohepatitis (IMCH) with steroid-dependence successfully treated with tocilizumab combined with mycophenolate mofetil (MMF). Case Description/Methods: A 53-year-old woman with a history of right breast cancer treated with neoadjuvant carboplatin/paclitaxel and an ICI, pembrolizumab, developed new-onset CTCAE grade 4 liver injury. After 2 cycles of pembrolizumab, her liver enzymes increased to initial peak alanine aminotransferase (ALT) 1,037 U/L, aspartate aminotransferase 686 U/L, and alkaline phosphatase 534 U/L, without liver synthetic dysfunction. Although liver enzymes initially improved after starting oral prednisone 100 mg/d (1.8 mg/kg/d) for 4 days and 75 mg/d (1.4 mg/kg/d), across 2 weeks, attempted taper to oral budesonide 9 mg/d led to resurgence of ALT to 873 U/L. After diagnostic liver biopsy confirmed IMCH, induction intravenous (IV) methylprednisolone (MP) 60 mg/d and IV tocilizumab (TCZ) 8 mg/kg were administered, but subsequent prednisone taper did not yield remission. Due to necessity of right segmental mastectomy, high-dose steroids were avoided peri-operatively. A week post-surgery, MMF and budesonide 9 mg/d were initiated, followed by IV MP re-induction and IV TCZ 8 mg/kg, without adverse events. After 2 weeks of budesonide 6 mg/d and 2 weeks of 3 mg/d, with cessation of MMF, she achieved complete and sustained biochemical remission. Discussion: Society guidance documents have proposed a variety of steroid-sparing adjunctive treatment options for managing steroid-refractory/steroid-dependent IMH, and TCZ has emerged as an attractive option. Use of TCZ can free a patient from steroid-dependency. One or 2 total infusions of TCZ is sufficient. We predicted that our patient would develop a protracted course of immunosuppressive need and steroid-refractoriness based on the phenotype (IMCH), prompting utilization of TCZ; MMF acted as a simultaneous bridge from systemic steroids. We also favored budesonide over prednisone to decrease the cumulative exposure to systemic steroids, especially in the peri-operative period.