Daratumumab

Mechanism of action

◆CD38, a surface glycoprotein abundant on myeloma plasma cellsDaratumumab

ⓘ The crystal shows the extracellular domain of human CD38 bound to the antigen-binding fragment of daratumumab.

Daratumumab is a human IgG1 antibody that binds CD38 on the surface of myeloma cells and other blood cells. The bound antibody recruits complement (complement-dependent cytotoxicity) and immune effector cells such as natural killer cells (antibody-dependent cellular cytotoxicity), which kill the tumour cell. Because it is given with other myeloma drugs, its effect adds to theirs.

1. Daratumumab binds CD38 on myeloma cells
2. Complement and NK cells are drawn to the coated cell
3. The myeloma cell is destroyed

Indications

• Multiple myeloma, newly diagnosed or relapsed, alone or with other drugs such as lenalidomide or bortezomib and dexamethasone. Multiple myeloma →
• The subcutaneous form is also used, with other drugs, in a type of amyloidosis in newly diagnosed adults. Amyloidosis →

Adverse effects

Common

• Infusion reactions: cough, wheeze, throat tightness, stuffy nose, chills
• Upper respiratory infections
• Tiredness, back and joint pain, muscle spasms
• Diarrhoea, constipation, swelling of the legs
• Tingling or burning in the hands and feet

Contraindications

• Previous severe allergy to daratumumab or its ingredients

Key interactions

Blood-bank compatibility tests (indirect antiglobulin test, crossmatch)

Daratumumab can give false results for up to six months after the last dose; blood typing is done before the first dose and the blood bank is told.

Other laboratory tests

It can change the results of some tests, so the laboratory is told the patient receives it.

What is monitored

• Vital signs and breathing during and after each infusion
• Blood count
• Blood type and antibody screen before the first dose
• Hepatitis B history and signs of infection or shingles

Administration and safety

• Given by a doctor or nurse in a healthcare setting, with medicines before and after the infusion to prevent reactions.
• The intravenous and subcutaneous (with hyaluronidase) products are different preparations and are not interchanged.
• The infusion may be slowed or stopped if a reaction occurs.

Pregnancy and breastfeeding

Contraception is used during treatment and for some months after the last dose.

Nursing care

• Watch closely during the infusion and afterwards for cough, wheeze, throat tightness or breathlessness.
• Before any transfusion, tell the blood bank that the patient receives or received daratumumab.
• Ask about hepatitis B, shingles, asthma or COPD before starting.
• Teach the patient to report fever, bruising, bleeding or yellow skin.

Pharmacokinetics

Absorption

Intravenous infusion; another form is injected under the skin together with hyaluronidase.

Elimination

Like other IgG antibodies, it is broken down by protein catabolism rather than by the liver or kidneys.

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Connections

← Back to the class: Antineoplastic monoclonal antibodies

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Daratumumab Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2019); Daratumumab and Hyaluronidase-fihj Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2024); crystal structure of CD38 in complex with daratumumab (RCSB Protein Data Bank, 2021).

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Representative model, for educational purposes only.