Trastuzumab Emtansine-Induced Nodular Regenerative Hyperplasia: Is Dose Reduction Enough as a Preventable Measure?

Trastuzumab emtansine (T-DM1) is a novel antibody-drug conjugate targeting the human epidermal growth factor receptor 2, used in some recurrent metastatic cancers. It was linked to modest increases in serum aminotransferase elevations and bilirubin. More recently, some cases of noncirrhotic portal hypertension have been described in patients on long-term T-DM1. The underlying liver condition is usually nodular regenerative hyperplasia (NRH) with elements of sinusoidal obstruction.

We report the case of a 52-year-old woman who started T-DM1 therapy for recurrent metastatic lung adenocarcinoma. Although a progressive reduction in lung nodules was noticed, there was a new-onset cytocholestasis and elevation in bilirubin. A reduction in platelet count was also apparent over several months during the T-DM1 therapy. Liver biopsy revealed NRH and so the dose of T-DM1 was reduced. Thereafter, the patient had normalization of liver tests and platelet count. T-DM1 was continued for more than 9 months with no signs of portal hypertension or cancer progression.

We presented a rare case of NRH induced by T-DM1 in a patient with lung adenocarcinoma. A high index of suspicion for liver injury and NRH must be maintained for patients who develop liver test abnormalities and/or signs of portal hypertension during treatment with T-DM1. This is the first report of a successful dose reduction in a patient with NRH induced by T-DM1, suggesting that it is possible to maintain the drug while it is being effective for lung cancer treatment.