P3059 - Mycophenolate - A Treatment Option in Steroid Refractory Hepatitis Associated With Immune Checkpoint Inhibitors

Shreya Shambhavi, MD¹, Mariela Di Vanna, MD², Saria Qaiser, MD¹, Chirag Shah, MD^3
1RWJBH Rutgers Health/Community Medical Center, Toms River, NJ; ²RWJBH Rutgers Health Community Medical Center, Toms River, NJ; ³RWJBH Rutgers Health/ Community Medical Center, Toms River, NJ

Introduction: Hepatotoxicity associated with immune checkpoint inhibitors (ICI) is commonly characterized by elevation of aminotransferases, often leading to immunotherapy failure. Low-grade hepatitis usually responds to corticosteroids, but high-grade hepatitis often requires additional immunosuppressants like mycophenolate mofetil (MMF), azathioprine. With limited literature on MMF dosage, we describe a case series of steroid refractory ICI-related hepatotoxicity managed with MMF.

Case Description/Methods: 75-year-old female with lung adenocarcinoma on cycle 4 of pembrolizumab experienced grade 4 hepatitis. Oral prednisone was initiated at 2 mg/kg/day. With minimal improvement after 3 days, oral MMF 1 g b.i.d. was added to the regimen. Serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase (ALT, AST, ALP) normalized over 16 weeks. MMF was weaned at 1g q.a.m. and 500 mg q.h.s. for 8 weeks followed by 500 mg b.i.d. for 4 weeks and then to 250 mg b.i.d. over the next 4 weeks. Following the cessation of MMF, liver enzymes up trended even on low dose prednisone. MMF at 250 mg b.i.d. was reinitiated for an additional 4 weeks, after which resolution was noted.



81-year-old female with lung squamous cell carcinoma on cycle 3 of atezolizumab experienced grade 3 hepatitis. Oral prednisone was initiated at 2 mg/kg/day. With minimal improvement after 3 days, MMF 1g b.i.d. was added to the regimen. Serum aminotransferases normalized over 6 weeks. MMF was weaned at 1g q.a.m. and 500 mg q.h.s. for 6 weeks followed by 500 mg b.i.d. for 8 weeks.


74-year-old male with malignant melanoma on cycle 2 of nivolumab and ipilimumab experienced grade 2 hepatitis. Oral Prednisone was initiated at the dose of 0.5 mg/kg/day after which serum ALT normalized. After reinitiation of nivolumab monotherapy, grade 2 hepatitis occurred even on low dose prednisone. MMF was initiated at 500 mg b.i.d. dose and the patient’s liver enzymes normalized over a period of 6 weeks.

Discussion: Mycophenolate, in addition to steroids, prompts a more rapid decline in aminotransferases. We successfully tapered the dose of MMF over a period of 6 to 8 weeks with the decline in AST being most rapid followed by ALT, ALP. In one patient, hepatitis recurred after stopping MMF which was managed with reinitiation of MMF indicating that liver enzymes should be monitored on low-dose MMF even after their normalization rather than abrupt cessation. Further studies are needed for established guidelines regarding MMF dosing and its tapering.


Disclosures:


Shreya Shambhavi, MD¹, Mariela Di Vanna, MD², Saria Qaiser, MD¹, Chirag Shah, MD³. P3059 - Mycophenolate - A Treatment Option in Steroid Refractory Hepatitis Associated With Immune Checkpoint Inhibitors, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.