Drug Action
Daratumumab is a monoclonal antibody that binds to CD38, a cell-surface protein, resulting in tumour cell death by immune-mediated actions and apoptosis.
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Drug reference
Daratumumab is a monoclonal antibody that binds to CD38, a cell-surface protein, resulting in tumour cell death by immune-mediated actions and apoptosis.
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Multiple myeloma (as monotherapy after failure of a proteasome inhibitor and an immunomodulatory agent) (specialist use only) | Multiple myeloma (in combination with lenalidomide and dexamethasone in patients who have received at least one prior therapy) (specialist use only) ▶BY INTRAVENOUS INFUSION ▶Adult: 16 mg/kg once weekly for weeks 1 to 8, for week 1, dose can alternatively be divided over 2 consecutive days, then 16 mg/kg every 2 weeks for weeks 9 to 24, then 16 mg/kg every 4 weeks for week 25 onwards until disease progression, for dose interruption or infusion rate reduction due to infusion-related reactions or side-effects—consult product literature Multiple myeloma (in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy) (specialist use only) ▶BY INTRAVENOUS INFUSION ▶Adult: 16 mg/kg once weekly for weeks 1 to 9, for week 1, dose can alternatively be divided over 2 consecutive days, then 16 mg/kg every 3 weeks for weeks 10 to 24, then 16 mg/kg every 4 weeks for week 25 onwards until disease progression, for dose interruption or infusion rate reduction due to infusion-related reactions or side-effects—consult product literature Newly diagnosed multiple myeloma (in combination with bortezomib, melphalan and prednisone) (specialist use only) ▶BY INTRAVENOUS INFUSION ▶Adult: 16 mg/kg once weekly for weeks 1 to 6, for week 1, dose can alternatively be divided over 2 consecutive days, then 16 mg/kg every 3 weeks for weeks 7 to 54, then 16 mg/kg every 4 weeks for week 55 onwards until disease progression, for dose interruption or infusion rate reduction due to infusion-related reactions or side-effects—consult product literature
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History of obstructive pulmonary disorder (consider additional post-medication—consult product literature). patients may need pre-medication to minimise adverse reactions. risk of herpes zoster reactivation (consider antiviral prophylaxis) CAUTIONS, FURTHER INFORMATION ▶Infusion-related reactions Serious infusion-related reactions can occur and daratumumab should only be administered when appropriately trained staff and resuscitation facilities are immediately available; manufacturer advises pre-medication with a corticosteroid, an antihistamine and an anti-pyretic and post-medication with oral corticosteroids—consult product literature. Manufacturer advises patients should be closely monitored for signs of infusion-related reactions during and after administration; in the event of a hypersensitivity reaction, treatment should be stopped immediately and appropriate management initiated. Immune system and malignant disease
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NICE decisions ▶Daratumumab monotherapy for treating relapsed and refractory multiple myeloma (March 2018) NICE TA510 Daratumumab (Darzalex ®) monotherapy is recommended for use within the Cancer Drugs Fund as an option for treating relapsed and refractory multiple myeloma in adults whose previous therapy included a proteasome inhibitor and an immunomodulator, and whose disease progressed on the last therapy, only if: . they have daratumumab after 3 previous therapies, and . the conditions in the managed access agreement are followed. Patients whose treatment was started within the NHS before this guidance was published should have the option to continue treatment, without change to their funding arrangements, until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta510 ▶Daratumumab with bortezomib and dexamethasone for previously treated multiple myeloma (April 2019) NICE TA573 Daratumumab (Darzalex ®) plus bortezomib plus dexamethasone is recommended for use within the Cancer Drugs Fund as an option for treating relapsed multiple myeloma in people who have had one previous treatment. It is recommended only if the conditions in the managed access agreement for daratumumab plus bortezomib plus dexamethasone are followed. Patients whose treatment was started within the NHS before this guidance was published should have the option to continue treatment, without change to their funding arrangements, until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta573 Scottish Medicines Consortium (SMC) decisions SMC No. 1205/17 The Scottish Medicines Consortium has advised (October 2017) that daratumumab (Darzalex ®) is accepted for Immune system and malignant disease restricted use within NHS Scotland as monotherapy for use as a fourth-line treatment option for adults with relapsed and refractory multiple myeloma, only if a proteasome inhibitor and an immunomodulatory agent have been used as prior therapy and disease demonstrated progression on the last therapy. This advice is contingent upon the continuing availability of the patient access scheme in NHS Scotland or a list price that is equivalent or lower. SMC No. SMC2180 The Scottish Medicines Consortium has advised (July 2019) that daratumumab (Darzalex ®) is accepted for restricted use within NHS Scotland when used in combination with bortezomib and dexamethasone, for the treatment of adults with multiple myeloma who have received one prior therapy only.
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MHRA/CHM ADVICE: DARATUMUMAB (DARZALEX ®): RISK OF REACTIVATION OF HEPATITIS B VIRUS (AUGUST 2019) An EU cumulative review of worldwide data has identified reports of hepatitis B virus (HBV) reactivation in patients treated with daratumumab, including several fatal cases. Healthcare professionals are advised to screen all patients for hepatitis B before starting treatment; patients with unknown serology already being treated with daratumumab should also be screened. Those with positive serology should be monitored for signs of HBV reactivation during, and for at least 6 months after, treatment; immediate medical attention should be sought if signs and symptoms of HBV reactivation develop. Daratumumab should be stopped in patients with HBV reactivation and appropriate treatment initiated, based on expert advice. Experts should be consulted before resuming daratumumab in patients with adequately controlled viral reactivation.
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→Appendix 1: monoclonal antibodies
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▶Common or very common Anaemia. atrial fibrillation. cough. diarrhoea. dyspnoea. fatigue. fever. headache. hypertension. increased risk of infection. infusion related reaction. lymphopenia. muscle spasms. nausea. neutropenia. peripheral neuropathy. peripheral oedema. pulmonary oedema. thrombocytopenia. vomiting ▶Uncommon Hepatitis B reactivation ▶Rare or very rare Anaphylactic reaction SIDE-EFFECTS, FURTHER INFORMATION Manufacturer advises treatment should be immediately interrupted if an infusion-related reaction of any grade or severity occurs— consult product literature for specific management recommendations.
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Manufacturer advises effective contraception in women of childbearing potential during treatment and for 3 months after stopping treatment. See also Pregnancy and reproductive function in Cytotoxic drugs p. 938.
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Manufacturer advises avoid unless potential benefit outweighs risk—no information available. See also Pregnancy and reproductive function in Cytotoxic drugs p. 938.
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Manufacturer advises avoid—no information available. l EFFECT ON LABORATORY TESTS Possible positive indirect Coombs test (may affect antibody screening). l HANDLING AND STORAGE Manufacturer advises store in a refrigerator at 2–8°C; consult product literature for storage advice following dilution.
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There can be variation in the licensing of different medicines containing the same drug. Solution for infusion EXCIPIENTS: May contain Polysorbates ELECTROLYTES: May contain Sodium ▶Darzalex (Janssen-Cilag Ltd) A Daratumumab 20 mg per 1 ml Darzalex 400mg/20ml concentrate for solution for infusion vials | 1 vial P £1,440.00 (Hospital only) Darzalex 100mg/5ml concentrate for solution for infusion vials | 1 vial P £360.00 (Hospital only)
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16 mg/kg once weekly for weeks 1 to 8, for week
First-line fragment. Read the complete Indications and Dose section above.
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16 mg/kg once weekly for weeks 1 to 9, for week
First-line fragment. Read the complete Indications and Dose section above.
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16 mg/kg once weekly for weeks 1 to 6, for week
First-line fragment. Read the complete Indications and Dose section above.
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