Antibody-Drug Conjugates: The Toxicities and Adverse Effects That Emergency Physicians Must Know.

Abstract

Antibody-drug conjugates are novel antineoplastic agents whose use is expanding, both in terms of the number of drugs and the number of patients being treated. This article reviews the known toxicities and complications of antibody-drug conjugates that are currently approved for the treatment of cancer in the United States, with a focus on their emergency presentation and management. Similar to many other cancer therapies, most antibody-drug conjugates can cause diarrhea, nausea/vomiting, rash, peripheral neuropathy, and cytopenia, which are generally treated following standard-of-care. Interstitial lung disease, which may mimic pneumonia and cause respiratory failure and death, has been seen with trastuzumab deruxtecan and mirvetuximab soravtansine; emergency treatment of this condition includes oxygenation, ventilatory support, and corticosteroids. Inotuzumab ozogamicin and gemtuzumab ozogamicin are both associated with sinusoidal obstruction syndrome, a potentially fatal liver dysfunction that presents with weight gain, fluid overload, and jaundice. Abnormal liver function tests in patients who have been recently treated with these agents should be cautiously evaluated. Cardiac adverse events with antibody-drug conjugates are rare, but trastuzumab emtansine and trastuzumab deruxtecan may cause a decrease in cardiac contractility, and heart rate corrected QT interval prolongation is a rare effect of trastuzumab deruxtecan. Ocular adverse events, especially blurred vision, and keratopathy, are common with mirvetuximab soravtansine and tisotumab vedotin. Progressive multifocal leukoencephalopathy has been reported with brentuximab vedotin and polatuzumab vedotin. Tumor lysis syndrome may occur after treatment with gemtuzumab ozogamicin, polatuzumab vedotin, and brentuximab vedotin. Patients receiving enfortumab vedotin or brentuximab vedotin may develop hyperglycemia, sometimes presenting as diabetic ketoacidosis. Tisotumab vedotin and trastuzumab emtansine are associated with bleeding; although it is minor in most cases, severe bleeding and intracranial hemorrhage have occurred. Several antibody-drug conjugates can cause an anaphylactoid infusion-related reaction, which occurs most commonly during or soon after infusion but may be delayed up to 24 hours. Further research is needed to establish the real-world incidence of rare complications and how often patients with these complications present to the emergency department.