Daratumumab

Class
Targeted therapy
Subclass
Anti-CD38 monoclonal antibodies
Substance name
Daratumumab
Brand names
Darzalex®
Common formulations
Concentrate for injectable solution
Dosage and administration
Adults patients
Multiple myeloma • Newly diagnosed, transplant-eligible
•
Start at: 16 mg/kg IV weekly for weeks 1-8, followed by 16 mg/kg IV q2 weeks for weeks 9-16 (induction), then stopped for high-dose chemotherapy and transplantation
•
Maintenance: 16 mg/kg IV q2 weeks for weeks 1-8 (consolidation)
Administered in combination with bortezomib, thalidomide, and dexamethasone (D-VTd).
Multiple myeloma • Newly diagnosed, transplant-ineligible
•
Start at: 16 mg/kg IV weekly for weeks 1-8, followed by 16 mg/kg IV q2 weeks for weeks 9-24
•
Maintenance: 16 mg/kg IV q4 weeks until disease progression
Administered in combination with lenalidomide and dexamethasone (DRd).
Multiple myeloma • Newly diagnosed, transplant-ineligible
•
Start at: 16 mg/kg IV weekly for weeks 1-6, followed by 16 mg/kg IV q3 weeks for weeks 7-54
•
Maintenance: 16 mg/kg IV q4 weeks until disease progression
Administered in combination with bortezomib, melphalan, and prednisone (D-VMP).
Multiple myeloma • Relapsed or refractory, after 1 or more prior lines of therapy
•
Start at: 16 mg/kg IV weekly for weeks 1-9, followed by 16 mg/kg IV q3 weeks for weeks 10-24
•
Maintenance: 16 mg/kg IV q4 weeks until disease progression
Administered in combination with bortezomib and dexamethasone (DVd).
Multiple myeloma • Relapsed or refractory, after 1 or more prior lines of therapy
•
Start at: 16 mg/kg IV weekly for weeks 1-8, followed by 16 mg/kg IV q2 weeks for weeks 9-24
•
Maintenance: 16 mg/kg IV q4 weeks until disease progression
Administered in combination with lenalidomide and dexamethasone (DRd).
Multiple myeloma • Relapsed or refractory, after at least 2 prior lines of therapy including lenalidomide and a proteasome inhibitor
•
Start at: 16 mg/kg IV weekly for weeks 1-8, followed by 16 mg/kg IV q2 weeks for weeks 9-24
•
Maintenance: 16 mg/kg IV q4 weeks until disease progression
Administered in combination with pomalidomide and dexamethasone (DPd).
Multiple myeloma • Relapsed or refractory, after 1-3 prior lines of therapy
•
Loading: 8 mg/kg IV q24h for days 1 and 2
•
Subsequently: 16 mg/kg IV weekly for weeks 2-8, followed by 16 mg/kg IV q2 weeks for weeks 9-24
•
Maintenance: 16 mg/kg IV q4 weeks until disease progression
Administered in combination with carfilzomib and dexamethasone (DKd).
Multiple myeloma • Relapsed or refractory, double-refractory to a proteasome inhibitor and an immunomodulatory agent, monotherapy
•
Start at: 16 mg/kg IV weekly for weeks 1-8, followed by 16 mg/kg IV q2 weeks for weeks 9-24
•
Maintenance: 16 mg/kg IV q4 weeks until disease progression
Multiple myeloma • Relapsed or refractory, after at least 3 prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent, monotherapy
•
Start at: 16 mg/kg IV weekly for weeks 1-8, followed by 16 mg/kg IV q2 weeks for weeks 9-24
•
Maintenance: 16 mg/kg IV q4 weeks until disease progression
Indications for use
Labeled indications
Adults
•
Treatment of multiple myeloma (newly diagnosed, transplant-eligible)
•
Treatment of multiple myeloma (newly diagnosed, transplant-ineligible)
•
Treatment of multiple myeloma (relapsed or refractory)
•
Treatment of multiple myeloma (relapsed or refractory, after 1 or more prior lines of therapy)
•
Treatment of multiple myeloma (relapsed or refractory, after 1-3 prior lines of therapy)
•
Treatment of multiple myeloma (relapsed or refractory, after at least 2 prior lines of therapy including lenalidomide and a proteasome inhibitor)
•
Treatment of multiple myeloma (relapsed or refractory, after at least 3 prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent, monotherapy)
•
Treatment of multiple myeloma (relapsed or refractory, double-refractory to a proteasome inhibitor and an immunomodulatory agent, monotherapy)
Safety risks
Contraindications
Hypersensitivity to daratumumab or its components
Warnings and precautions
Acute exacerbations of COPD
•
Use caution in patients with COPD. Consider administering post-infusion short- and long-acting bronchodilators and ICSs.
Decreased blood neutrophil count, decreased platelet count
•
Maintain a high level of suspicion, as daratumumab can increase neutropenia and thrombocytopenia induced by background therapy. Monitor CBC.
Infusion-related reactions
•
Maintain a high level of suspicion, as daratumumab has been associated with an increased risk of severe and/or serious infusion-related reactions, including anaphylactic reactions. Administer corticosteroids, acetaminophen, and diphenhydramine 1-3 hours before infusion for premedication, along with post-infusion corticosteroids.
Interference with determination of treatment response
•
Maintain a high level of suspicion, as daratumumab is a human IgG kappa monoclonal antibody and can interfere with determination of complete response and disease progression in patients with IgG kappa myeloma protein.
Positive indirect Coombs test
•
Maintain a high level of suspicion, as daratumumab binds to CD38 on RBCs and may results in a false-positive indirect Coombs test.
Reactivation of herpes zoster
•
Maintain a high level of suspicion, as daratumumab has been reported to cause reactivation of herpes zoster. Initiate antiviral prophylaxis for herpes zoster reactivation within 1 week after starting and continue for 3 months after treatment.
Specific populations
Renal impairment
CrCl ≥ 15 mL/min
•
Use acceptable. No dose adjustment required.
CrCl < 15 mL/min
•
No guidance available.
Renal replacement therapy
Any modality
•
No guidance available.
Hepatic impairment
Child-Pugh A (mild)
•
Use acceptable. No dose adjustment required.
Child-Pugh B (moderate)
•
Use acceptable. No dose adjustment required.
Child-Pugh C (severe)
•
No guidance available.
Pregnancy and breastfeeding
Pregnancy
All trimesters • Australia Category: C
•
Do not use. Evidence of fetal harm in humans. Daratumumab may cause fetal harm based on the mechanism of action. Advise female patients of reproductive potential to use effective contraception during treatment and for 3 month after the last dose.
Breastfeeding
Do not use during breastfeeding.
Unknown amount excreted in breastmilk.
Unknown drug levels in breastfed infants.
Adverse reactions
Very common > 10%
•
Anemia, ↓ blood lymphocyte count, ↓ blood neutrophil count, ↓ platelet count, infusion-related reactions, nasopharyngitis, pneumonia, arthralgia, back pain, chest pain, constipation, cough, diarrhea, dyspnea, fatigue, fever, headache, loss of appetite, nasal congestion, nausea, pain in extremity, vomiting, upper respiratory tract infections
Common 1-10%
•
Hepatitis B virus infection, herpes zoster, hypertension, chills
Unknown frequency
•
Anaphylaxis, acute pancreatitis, cytomegalovirus infection, listeriosis, syncope
Interactions
Drug(s)
Check Interactions
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