Evaluation of mycophenolic acid exposure in a patient with immune-related hepatotoxicity caused by nivolumab and ipilimumab therapy for malignant melanoma: a case report.

BACKGROUND: Guidelines such as the National Comprehensive Cancer Network recommend mycophenolate mofetil (MMF) for the treatment of severe steroid-refractory immune-related hepatotoxicity. Mycophenolic acid (MPA) is an active form of MMF that suppresses T- and B-lymphocyte proliferation and immune-related adverse events caused by immune checkpoint inhibitors. MPA has a narrow therapeutic range (37-70 µg·h/mL) and overexposure increases the risk of leukopenia in transplantation. However, the optimal use of MMF in oncology has not yet been established; thus, monitoring plasma MPA concentrations is necessary to avoid excessive immunosuppression in oncology practice. CASE PRESENTATION: We evaluated plasma MPA concentration in a 75-year-old man with immune-related hepatotoxicity following nivolumab and ipilimumab combination therapy for malignant melanoma. The patient developed severe hepatotoxicity after immunotherapy, and immunosuppressant therapy with corticosteroids was initiated. The patient then developed steroid-refractory immune-related hepatotoxicity; therefore, MMF (1,000 mg twice daily) was co-administered. Seven days after the administration of MMF, the plasma MPA concentration was measured using an enzyme multiplied immunoassay technique. The area under the plasma concentration-time curve for MPA from 0 to 12 h was 41.0 µg·h/mL, and the same dose of MMF was continued. Grade 2 lymphocytopenia, which could be attributed to MMF, was observed during the administration period. Unfortunately, the patient was infected with SARS-CoV-2 and died from respiratory failure. CONCLUSION: Our patient did not exceed the upper limit of MPA levels as an index of the onset of side effects of kidney transplantation and achieved rapid improvement in liver function. Prompt initiation of MMF after assessment of the steroid effect leads to adequate MPA exposure. Therapeutic drug monitoring should be considered when MMF is administered, to avoid overexposure.

Unusual atrophic change after repeated arterial therapy for hepatocellular carcinoma: report of a case.

We report the case of a 45-year-old man with advanced hepatocellular carcinoma (HCC) who was able to undergo radical surgery after repeated transarterial therapy. Transarterial chemoembolization was repeated three times, and thereafter, transarterial infusion chemotherapy using Lipiodol was performed on the right hepatic artery. Because notable atrophy of the right lobe and compensated hypertrophy of the left lobe were detected after this therapy, an extended right lobectomy could be performed. Histologically, the HCC showed complete necrosis. The remarkable atrophic change of the right lobe was thought to be due to an obstruction of the right portal veins by the spread of inflammation around the bile duct necrosis, in addition to the narrowing of the hepatic artery. A thorough understanding of this phenomenon and the development of methods to clinically apply it in the treatment of cancer patients may thus lead to an increase in the percentage of resectable cases of advanced HCC.