Ipilimumab/nivolumab/prednisolone

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

A 62-year-old man developed nephritis during treatment with ipilimumab and nivolumab for metastatic renal cell cancer (RCC). Additionally, he developed rebound renal failure following rapid dose reduction of prednisolone.

The man, with metastatic RCC, started receiving first-line treatment with 3-weekly ipilimumab 1 mg/kg plus nivolumab 3 mg/kg. Additionally, he had been receiving unspecified low molecular weight heparins for paraneoplastic pulmonary embolism. After achieving clinical benefit, maintenance therapy with nivolumab 2 weekly was started. However, after 3 cycles, creatinine levels increased from 126 µmol/L to 265 µmol/L and the estimated glomerular filtration rate (eGFR) decreased from 53 mL/min to 21 mL/min, which was accompanied by erythrocyturia and proteinuria. Based on the finding, he was diagnosed with grade II nephritis secondary to ipilimumab and nivolumab.

The man was then treated with prednisolone 1 mg/kg daily, and maintenance therapy with nivolumab was discontinued. In March 2020, he was hospitalised due to COVID-19. At the time of hospital admission (2 days after the onset of symptoms), he had been treated with prednisolone for 4 weeks, and the last dose of nivolumab had been administered 6 weeks earlier. At that time, his creatinine level was decreased to 163 µmol/L with an eGFR of 38 mL/min. Thereafter, prednisolone was rapidly reduced to 60mg daily within 3 days [routes not stated]. This prednisolone dose reduction was accompanied by a grade IV renal failure (creatinine 500 µmol/L and eGFR 10 mL/min) [time to reactions onset stated]. Thus, he was treated with high dose prednisolone. Additionally, he received empiric antibiotic therapy with cefuroxime and azithromycin, along with minimal oxygen therapy for a few days. Following 12 days of admission, he was discharged. However, he was re-admitted within 7 days due to clinical deterioration. Thereafter, he developed brain metastasis and severe neurological deterioration. Eventually, he died [not all outcomes stated].