Low serum concentrations of bevacizumab and nivolumab owing to excessive urinary loss in patients with proteinuria: a case series.

Abstract

Proteinuria can cause interindividual variability in the pharmacokinetics of therapeutic antibodies and may affect therapeutic efficacy. Here, we measured the serum and urinary concentrations of bevacizumab (BV) and nivolumab (NIVO) in patients with proteinuria and reported a case series of these patients. Thirty-two cancer patients who received BV every 3 weeks or NIVO every 2 weeks between November 2020 and September 2021 at Kyoto University Hospital were enrolled in this study. The serum and urinary concentrations of BV and NIVO were measured using liquid chromatography-tandem mass spectrometry. We divided the BV-treated patients and the NIVO-treated patients into two groups based on the urine protein-creatinine ratio (UPCR): UPCR 1g/g or higher (BV, n = 9; NIVO, n = 3) and UPCR less than 1g/g (BV, n = 14; NIVO, n = 6). Serum concentrations of the therapeutic antibodies adjusted by their doses were significantly lower in both BV- and NIVO-treated patients with UPCR 1g/g or higher compared to those with less than 1g/g. In patients with UPCR 1g/g or higher, urinary concentrations of the therapeutic antibodies adjusted by their serum concentrations and urinary creatinine concentrations tended to increase. This case-series study suggests a possibility of reduction in serum concentrations of BV and NIVO in patients with proteinuria by urinary excretion of these drugs.