Stage IV lung adenocarcinoma with paraneoplastic nephrotic syndrome during pembrolizumab therapy

What happened, in summary

This 68-year-old man was diagnosed in December 2021 with left lung non-small cell lung cancer adenocarcinoma, cT3N3M1c, with brain metastases. Tumor testing showed PD-L1 tumor proportion score greater than 50% and a KRAS exon 3 mutation; next-generation sequencing and FISH did not find a target suitable for first-line targeted therapy. The treatment plan included cranial stereotactic radiation followed by pembrolizumab monotherapy. Before immunotherapy began, he was hospitalized for Streptococcus pneumoniae pneumonia. During that admission, edema, severe hypoalbuminemia, and proteinuria led to kidney biopsy, which diagnosed paraneoplastic membranous nephropathy causing nephrotic syndrome. Pembrolizumab was started at 200 mg every 3 weeks, with the expectation that treating the lung cancer could also improve the paraneoplastic kidney problem. Because nephrotic syndrome can theoretically cause urinary loss of large protein drugs, his team measured pembrolizumab levels in blood and urine. Pembrolizumab was not detected in 24-hour urine collections, and serum levels suggested adequate exposure. Edema improved with loop diuretics, serum albumin rose, and proteinuria decreased during treatment. Tumor evaluation after cycle 4 showed partial response by RECIST 1.1. After 6 months, national dosing guidance changed his pembrolizumab schedule to 4 mg/kg every 6 weeks. In September 2022, bone metastases progressed and were treated with radiation. Two months later, the right upper-lobe target lesion progressed. Pembrolizumab was stopped after 9 months total, and second-line carboplatin plus pemetrexed was started. The case is useful because it connects cancer response, kidney manifestations of paraneoplastic disease, and drug exposure monitoring in a patient receiving immune checkpoint therapy.