daratumumab (DAYR-uh-TOOM-yoo-mab)A drug used to treat multiple myeloma. It is used with dexamethasone and lenalidomide or bortezomib in patients whose cancer was treated with at least one anticancer therapy. It is used alone in patients whose cancer was treated with at least three anticancer therapies, including a proteasome inhibitor and an immunomodulating agent. It is also being studied in the treatment of other types of cancer. Daratumumab binds to a protein called CD38, which is found on some types of immune cells and cancer cells, including myeloma cells. Daratumumab may block CD38 and help the immune system kill cancer cells. It is a type of monoclonal antibody. Also called Darzalex.
Information about Daratumumab
Liver safety of Daratumumab
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.
Mechanism of action of Daratumumab
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.
FDA approval information for Daratumumab
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.
Dosage and administration for Daratumumab
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 of Daratumumab
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.