Background
Checkpoint inhibitors (CPIs) are used to treat a number of tumour types, including melanoma, lung and genitourinary cancers. Immune related adverse events (IRAEs) are a known risk of CPIs, with the potential for serious and permanent toxicity, including death. Whilst CPIs may be safely used in patients with pre-existing auto-immune conditions (AICs), this is generally in the setting of non-life-threatening AICs such as rheumatoid arthirtis1-3. We report the case of a patient with stage IV melanoma and primary biliary cholangitis(PBC)/autoimmune hepatitis (AIH) overlap, who was successfully treated with CPI therapy without exacerbation of her liver disease.
Case report
A 63yo female presented with cholestatic liver function tests; ALP 278U/L, GGT 408U/L, AST 52U/L, ALT 53U/L and bilirubin 6umol/L. Liver MRCP and fibroscan were normal. Autoantibodies showed positive ASMA, weak positive ANCA and negative AMA. Liver biopsy was consistent with PBC/AIH overlap syndrome. She was initially managed with ursodeoxycholic acid, with azathioprine added due to suboptimal disease control. In September 2019 the patient presented with a right axillary mass and was diagnosed with Stage III BRAF wild-type melanoma of unknown primary site. Axillary clearance was performed, azathioprine was ceased and regular surveillance was commenced. Adjuvant immunotherapy was not recommended due to the risk of worsening her AIH/PBC. Surveillance PET in March 2019 revealed metastatic disease in lymph nodes and soft tissues. She was commenced on pembrolizumab. Restaging PET after 4 cycles of treatment showed a complete metabolic response. She has now received 6 cycles, with no hepatitis or other significant toxicity.
Discussion
We believe this is the first reported case of the safe administration of pembrolizumab in a patient with known AIH/PBC. Further research into the optimal duration of treatment is needed, so as to maximise disease control whilst minimising side effects, especially in patients at increased risk of toxicity1-3.