Daratumumab

What it is and how it works

Daratumumab is a human IgG1κ monoclonal antibody that binds CD38, which is highly expressed on multiple myeloma cells. It kills tumour cells through complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity and phagocytosis, apoptosis, and depletion of CD38-positive immunosuppressive cells.

Indications

Multiple myeloma, newly diagnosed or relapsed/refractory, alone or in combination with other regimens (e.g. lenalidomide or bortezomib with dexamethasone); the subcutaneous formulation is also indicated for systemic AL amyloidosis.

Dosage and administration (summary)

Intravenous infusion 16 mg/kg or subcutaneous injection 1800 mg, given weekly initially, then every 2 weeks and subsequently every 4 weeks according to the combination regimen; pre-medication with a corticosteroid, antipyretic and antihistamine is required.

Contraindications

Hypersensitivity to daratumumab or to any excipient.

Warnings and precautions

Infusion-related and systemic administration reactions, including severe reactions, occur mainly with the first dose; pre- and post-medication and monitoring are required. Daratumumab binds CD38 on red cells and interferes with indirect antiglobulin (indirect Coombs) testing, so patients should be typed and screened before starting treatment and the blood bank informed. Neutropenia, thrombocytopenia, infections and hepatitis B reactivation may occur.

Pregnancy

Avoid in pregnancy unless benefit outweighs risk; women of childbearing potential should use effective contraception during and for 3 months after treatment.

Storage and supply

Store refrigerated at 2–8 °C, do not freeze, protect from light.

Source: reference summary prepared from the EU SmPC/EPAR, BNF and WHO Model Formulary. The approved product information in Iran governs.