Severe hepatitis arising from ipilimumab administration, following melanoma treatment with nivolumab

Abstract

After 4 weeks of the last dose of nivolumab, a 59-year-old man with stage IV melanoma was subject to treatment with ipilimumab. After 5 weeks, the patient developed severe hepatitis, showing markedly elevated levels of both aspartate aminotransferase and alanine aminotransferase (>2000 U/l). Using pulse steroid therapy with 1000 mg/d of methylprednisolone, liver function initially improved, but then deteriorated upon dosage reduction. Subsequently, mycophenolate mofetil (MMF) was administered at a dose of 2 g/d in addition to the corticosteroid, which resulted in aspartate aminotransferase and alanine aminotransferase levels gradually improving to grade 1, and the corticosteroid dose was successfully reduced to 0.5 mg/kg/d of oral prednisolone. Liver function then remained stable when MMF was tapered. In conclusion, the use of MMF improved liver function in this patient with steroid-refractory hepatitis induced by immune checkpoint inhibitor administration.

Secondary sclerosing cholangitis with hemobilia induced by pembrolizumab: Case report and review of published work

“…because of rapid disease progression; however, laboratory data showed only a slight improvement. Mycophenolate mofetil and anti‐tumor necrosis factor monoclonal antibody infliximab were reported as additional therapies for irAEs including hepatotoxicity or colitis . However, we could not obtain consent from the patient to try these additional therapies.…”

Acute Severe Autoimmune Hepatitis: Corticosteroids or Liver Transplantation?

“…With ipilimumab‐induced hepatitis, when a course of corticosteroids has failed, additional immunosuppression may be required with, eg, antithymocyte globulin or mycophenolate mofetil (MMF) . Notably, PD1 inhibitors are contraindicated in LT recipients due to the disruption in T cell pathways and increased episodes of rejection …”

“…(26,27) With ipilimumab-induced hepatitis, when a course of corticosteroids has failed, additional immunosuppression may be required with, eg, antithymocyte globulin or mycophenolate mofetil (MMF). (28,29) Notably, PD1 inhibitors are contraindicated in LT recipients due to the disruption in T cell pathways and increased episodes of rejection. (30,31) Although the mechanisms are not fully elucidated, antituberculous medications can induce hypersensitivity reactions, leading to B cell-mediated autoantibody production and cytotoxic T cell responses that resemble spontaneous idiopathic AIH.…”

Promises and challenges of immuno-oncology from a clinical perspective

“…The Japanese Journal of Clinical Oncology (JJCO) receives numerous manuscripts on cancer immunotherapy, and has published several original articles (4-6) as well as case reports (7)(8)(9)(10)(11)(12). In September 2015, we also published a review article on the 'current status of immunotherapy', in which Dr Suzuki and colleagues elegantly summarized the basic as well as clinical data of this emerging field (13).…”

“…It is reflected in the varieties of toxicities with immune-checkpoint inhibitors in JJCO case reports. In fact, all of the 'Case reports' on immunotherapies published in our journal were on their unique ir-AEs (7)(8)(9)(10)(11)(12). Therefore, in addition to hematology/oncology and immunology, we must have a broad knowledge of fields such as endocrinology, cardiology, nephrology, pulmonology, neurology and dermatology, to name just a few.…”