Background Pembrolizumab is a selective humanised IgG4 monoclonal antibody known as a programmed cell death 1 (PD-1) immune checkpoint inhibitor. It is the first PD-1 Inhibitor approved for unresectable or metastatic melanoma. With the arrival of this new mechanism of action, immune mediated adverse reactions have also been detected.
Purpose To describe immune mediated nephritis in a diagnosed nodular melanoma patient, treated with pembrolizumab as a secondline treatment.
Material and methods Data were obtained by review of the electronic medical records.
Results A 78-year-old man had a BRAF mutated metastatic nodular melanoma. He was included in the Columbus clinical trial and received a combination of BRAF inhibitor and MEK inhibitor as firstline treatment from April to September 2015. At that time, disease progression was determined by imaging tests. In October, the lesion was operated and patient received radiotherapy for 4 months. In March 2016, pembrolizumab was started as a secondline treatment, and was well tolerated at the beginning (cycles 1 and 2). After cycle 3, creatinine started to increase, reaching 3.59 (grade 3), and estimated glomerular filtration rate was 17.57 mL/min/1.73 m2. These laboratory abnormalities caused the patient’s emergency admission to hospital and treatment discontinuation. Renal function analytical parameters decreased to the normal range a month after treatment discontinuation.
Nephritis occurred in 0.4% of patients receiving pembrolizumab in the Trials keynote 001, 002 and 003. The median time to onset of nephritis was 5.1 months (range 12 days to 12.8 months). The Karch–Lasagna algorithm established a ‘possible’ relationship between nephritis and pembrolizumab treatment due to the existence of a temporal correlation between the facts.
Conclusion Health professionals must be vigilant in identifying drug related adverse reactions, particularly those related to drugs on the European list of medicinal products under additional monitoring. Nephritis has been reported in patients receiving pembrolizumab, and consequently patients should be monitored for changes in renal function, and other causes of renal dysfunction should be excluded. In our case, creatinine dramatically increased after the third cycle of treatment with pembrolizumab (onset of 3 months) and it has continuously decreased since pembrolizumab discontinuation, eventually reaching the normal range. This adverse reaction was reported to the national pharmacovigilance system.
References and/or acknowledgements European list of medicinal products under additional monitoring, 2016.
No conflict of interest
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