Management of lenvatinib induced nephrotic syndrome in a case of post liver transplant HCC reccurence

Background and Aim: Lenvatinib, a tyrosine kinase inhibitor, has been approved as first-line therapy for advanced HCC. Lenvatinib appears to be more effective in cancer control as compared to sorafenib. Adverse effects include hypertension, diarrhea, fatigue, decreased appetite, weight loss, stomatitis, hand-foot syndrome and proteinuria. Case Report: A 56-year-old male underwent live donor-related liver transplant for NASH-related CLD with HPS. Explant native liver specimen revealed HCC, pT2 (Pre transplant AFP 14ng/ml). He was on standard immunosuppressive regimen. PET imaging six months later revealed oligometastatic lesion in T10 vertebra. He received Locoregional therapy (SBRT) and Lenvatinib, dose was gradually up titrated to 12mg/day. After 9 months he developed worsening hypertension, hypoalbuminemia, pedal edema, hypertriglyceridemia, diarrhea, proteinuria (urine protein4+, urine 24 hours protein 9g/d), cataract, and hand-foot syndrome. After exclusion of all possible causes, Lenvatinib-induced nephrotic syndrome was diagnosed. Lenvatinib was discontinued and Sorafenib 400 mg/d was initiated. After Six weeks of discontinuing the drug, proteinuria reduced significantly. After 4 months of sorafenib therapy, most of the Lenvatinib induced adverse effects improved significantly including proteinuria (grade 4 to1), but lung nodules appeared with increased AFP levels. Sorafenib was continued, and locoregional therapy (SBRT) given. Follow-up imaging after six weeks showed new metastasis in the T9 vertebrae with further rise in AFP levels. Further SBRT was given and Lenvatinib was restarted at 4mg and up-titrated to 6mg/day. Post Lenvatinib decrease in AFP levels was noted. Conclusion: Proteinuria frequently reported adverse effect of Lenvatinib, it can occur any time after initiation and needs to be monitored. We report case of Lenvatinib-induced nephrotic syndrome in post-LDLT patient with metastatic HCC, with rapid resolution after drug discontinuation. Sorafenib was used instead and later he was switched back to Lenvatinib at lower dose due to disease progression and he is tolerating this does with AFP reduction.