Category/Class

Daratumumab is a CD38-directed cytolytic antibody, which is a type of immunotherapy.

Indications

Treatment (http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX-pi.pdf) of adult patients with multiple myeloma, as a monotherapy or in combination with other therapies

Dosing/Administration

IV infusion:

• Premedicate with corticosteroids, antipyretics, and antihistamines.
• Recommended dose is 16 mg/kg actual body weight. See full prescribing information for drugs used in combination and schedule
• Use a 0.22 or 0.2 mcm inline filter.
• Titrate per package insert based on volume and dose.
• Administer weekly for weeks 1–8, then every two weeks for weeks 9–24, and then every four weeks starting at week 25 until disease progression.
• Administer postinfusion medications.

SQ injection:

• Premedicate with corticosteroids, acetaminophen, and histamines.
• The dose is 1,800 mg daratumumab and 30,000 units hyaluronidase.
• To prevent needle clogging, attach the hypodermic injection needle or SQ infusion set to the syringe immediately prior to injection.
• Give SQ into the abdomen over approximately three to five minutes.
• Administer postinfusion medications.

Adverse Reactions

IV formulation: The most frequently reported (http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX-pi.pdf) adverse reactions (≥ 20%) were infusion reactions, neutropenia, thrombocytopenia, fatigue, asthenia, nausea, diarrhea, constipation, decreased appetite, vomiting, muscle spasms, arthralgia, back pain, pyrexia, chills, dizziness, insomnia, cough, dyspnea, peripheral edema, peripheral sensory neuropathy, bronchitis, pneumonia, and upper respiratory tract infection.

SQ formulation: The most frequently reported (http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf) adverse reaction (≥ 20%) as a monotherapy is upper respiratory tract infection. The most frequently reported adverse reactions with combination therapy (≥ 20%) are upper respiratory tract infection, constipation, nausea, fatigue, pyrexia, peripheral sensory neuropathy, diarrhea, cough, insomnia, vomiting, back pain, muscle spasms, pneumonia, and dyspnea. The most common hematology laboratory abnormalities (≥ 40%) are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin.

Nursing Considerations

IV formulation: Grade 1–2 reactions have occurred (http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX-pi.pdf) during the first infusion. Have immediate access to emergency equipment and appropriate medical support to manage infusion reactions. Frequently monitor patients during the entire infusion. Interrupt infusions for reactions, and permanently discontinue infusions for anaphylactic or life-threatening infusion reactions (https://www.ons.org/Chemotherapy-and-Immunotherapy-Guidelines-and-Recommendations-for-Practice).

Daratumumab binds to CD38 on red blood cells and results in a positive indirect Coombs test. All patients must receive a type and screen prior to starting therapy. Positive Coombs test may occur up to six months after the last administration. Notify the transfusion center that the patient has received daratumumab.

Daratumumab is contraindicated in patients with a history of severe hypersensitivity to the drug or any formulation components.

SQ formulation: Monitor for (http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf) hypersensitivity reactions. Monitor complete blood cell counts periodically during treatment. Monitor patients with neutropenia for signs of infection. Advise pregnant women of the risk to a fetus and advise females of reproductive potential to use effective contraception.

This formulation also binds to CD38 on red blood cells and results in a positive indirect Coombs test. All patients must receive a type and screen prior to starting therapy. Positive Coombs test may occur up to six months after the last administration. Notify the transfusion center that the patient has received daratumumab and hyaluronidase-fihj.

Patient Education

IV formulation: Infusion reactions are common (http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX-pi.pdf) and can be severe, but premedications will decrease their likelihood or severity. You will be monitored closely during your infusion.

Seek medical assistance right away if you experience shortness of breath or trouble breathing, dizziness or lightheadedness, cough, wheezing, throat tightness, runny or stuffy nose, headache, itching, nausea, vomiting, bruising, bleeding, chills, or fever.

Treatment can decrease your white blood cell and platelet counts, so your laboratory values will be monitored throughout treatment. Daratumumab can affect the results of blood tests to match your blood type for up to six months after your final dose of daratumumab. 

SQ formulation: Daratumumab and hyaluronidase-fihj may cause (http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf) serious allergic reactions. Tell your healthcare provider right away if you experience shortness of breath, dizziness, cough, wheezing, fast heartbeat, low oxygen, throat tightness, runny nose, headache, itching, high blood pressure, nausea, vomiting, chills, fever, or chest pain.

You might experience injection site reactions, including itching, swelling, bruising, or redness of the skin.

Treatment can decrease your white blood cell and platelet counts, so your laboratory values will be monitored throughout treatment. Daratumumab can affect the results of blood tests to match your blood type for up to six months after your final dose of daratumumab. 

Gero-Oncology Considerations

No overall differences in safety or effectiveness were observed between patients aged 65 or older and younger patients. Closely monitor for increased risk of infusion reaction and infection.

Safe Handling

Neither of the daratumumab formulations is considered hazardous.

Patient Assistance Program

A financial assistance program is available (https://www.darzalex.com/patient-financial-support).