Daratumumab is a human monoclonal antibody to CD38 which is used in combination with other antineoplastic agents in the therapy of multiple myeloma. Daratumumab has been implicated in instances of transient, mild-to-moderate serum enzyme elevations, but has not been linked to cases of clinically apparent liver injury with jaundice.


Daratumumab (dar" a toom' ue mab) is human IgG1 monoclonal antibody to CD38, which is a transmembrane glycoprotein that is frequently overexpressed on cancer cells including multiple myeloma cells. The monoclonal antibody binds to the CD38 molecule and triggers cell apoptosis, probably as a result of antibody mediated cytotoxicity. Daratumumab has been evaluated in heavily pretreated patients with refractory multiple myeloma and shown overall response rates of higher than expected. Daratumumab was given accelerated approval in the United States in 2015 for use in multiple myeloma. Current indications are as therapy of patients with refractory multiple myeloma in combination with lenalidomide (or bortezomib) and dexamethasone or as monotherapy in patients who have failed at least three previous regimens. Daratumumab is available as a solution for intravenous infusion in single use vials of 100 mg in 5 mL or 400 mg in 20 mL (20 mg/mL). The recommended dose is 16 mg/kg intravenously every week for 8 to 9 weeks, and then every 2, 3 or 4 weeks based upon indications and other agents being used. Premedication with methylprednisolone is recommended. Side effects are common and can include infusion reactions, bone marrow suppression, fatigue, nausea and vomiting, diarrhea, muscle spasms, back pain, fever, cough, dyspnea, peripheral edema, peripheral neuropathy and upper respiratory infection. Rare, but potentially serious side effects include severe infusion reactions, neutropenia, thrombocytopenia and interference with cross matching and red blood cell antibody screening.


In summary analyses of the registration trials of daratumumab for multiple myeloma, 15% of patients developed elevations in ALT during therapy, 13% alkaline phosphatase and 7% bilirubin. The abnormalities were generally mild-to-moderate, transient and asymptomatic. ALT elevations above 5 times the upper limit of normal occurred in less than 1% of patients. In these studies, daratumumab was given with lenalidomide and dexamethasone, and similar rates of liver enzyme elevations occurred with those agents alone without the monoclonal antibody. There were no instances of clinically apparent liver injury with jaundice attributable to daratumumab in these trials and no patient stopped therapy because of hepatic adverse events. Since its approval and more general use, there have been no published reports of clinically apparent liver injury due to daratumumab, and its product label does not list hepatotoxicity as an adverse event.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

Mechanism of Injury

The mechanism by which daratumumab might cause liver injury is not known. There is no evidence that CD38 is expressed on hepatocytes. Like other monoclonal antibodies, daratumumab is unlikely to have intrinsic hepatotoxicity, is metabolized to smaller peptides or amino acids by many cells, and does not affect the hepatic drug metabolizing enzymes or transporting molecules.

Outcome and Management

The liver injury attributed to daratumumab has invariably been self-limited and not associated with symptoms or jaundice. There is no information on possible cross sensitivity to the injury among different monoclonal antibodies or therapies directed at epidermal growth factor receptors.

Drug Class: Antineoplastic Agents, Monoclonal Antibodies



Daratumumab – Darzalex®


Antineoplastic Agents


Product labeling at DailyMed, National Library of Medicine, NIH



References updated: 25 May 2017

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