Drug Class:
- Monoclonal antibody — human IgG1κ
- CD38-directed cytolytic antibody
Mechanism of Action:
- Binds to CD38, a transmembrane glycoprotein highly expressed on plasma cells (including multiple myeloma cells).
- Induces cell death via:
- Complement-dependent cytotoxicity (CDC)
- Antibody-dependent cell-mediated cytotoxicity (ADCC)
- Antibody-dependent cellular phagocytosis (ADCP)
- Direct apoptosis through crosslinking.
- Also depletes CD38+ immunosuppressive regulatory cells → enhances T-cell function.
Oncology Indications:
- Multiple Myeloma (newly diagnosed and relapsed/refractory), alone or in combination with:
- Lenalidomide + dexamethasone (DRd)
- Bortezomib + melphalan + prednisone (DVMP)
- Bortezomib + dexamethasone (DVd)
- Carfilzomib + dexamethasone (DKd)
- Pomalidomide + dexamethasone (DPd)
- Light chain (AL) amyloidosis (with bortezomib + cyclophosphamide + dexamethasone).
Formulations & Dosing:
| Formulation | Route | Notes |
|---|---|---|
| Darzalex® | IV | Infuse over several hours; requires gradual rate escalation. First infusion can take 7+ hours. |
| Darzalex Faspro® | SC (subcutaneous) | Fixed-dose (1800 mg daratumumab + 30,000 units hyaluronidase) over 3–5 min; greatly reduces infusion time and reaction rates. |
Example IV Dosing (monotherapy or combo):
- 16 mg/kg IV weekly × 8 weeks → q2w × 16 weeks → q4w until progression or unacceptable toxicity.
Example SC Dosing:
- 1800 mg SC weekly × 8 → q2w × 16 → q4w until progression.
Key Toxicities / Warnings:
- Infusion-related reactions (IRRs) — most common with first dose (up to 50% IV, ~10% SC). Symptoms: nasal congestion, cough, throat irritation, dyspnea, chills, nausea.
- Myelosuppression — neutropenia, thrombocytopenia.
- Infections — bacterial/viral, risk ↑ with combination regimens.
- Interference with blood compatibility testing — daratumumab binds to CD38 on RBCs → panagglutination on indirect antiglobulin tests → may mask alloantibodies. Requires blood bank notification and pre-treatment type & screen.
- Hepatitis B reactivation — screen prior to therapy.
Premedication Recommendations (to prevent IRRs):
- Before IV:
- Corticosteroid (e.g., dexamethasone 20 mg IV)
- Antipyretic (acetaminophen 650–1000 mg PO)
- Antihistamine (diphenhydramine 25–50 mg PO/IV)
- After IV: Oral corticosteroid for 2 days post-dose to prevent delayed reactions.
- Before SC: Similar premeds recommended, but reactions are less frequent/severe.
Monitoring for Pharmacists:
- Vital signs during and after first dose.
- CBC periodically for cytopenias.
- HBV serology before starting; monitor for reactivation.
- Signs of infection.
- Blood type & screen before first dose, and inform transfusion services.
Drug Interactions:
- No CYP-mediated interactions; caution with other myelosuppressive or immunosuppressive agents.
Clinical Pearls:
- SC formulation is preferred for most patients due to shorter administration time, less IRR risk, and improved convenience.
- If IRR occurs with IV → pause, treat symptoms, restart at slower rate.
- Encourage patients to report any respiratory symptoms after first doses.
- For patients needing transfusion after starting therapy → coordinate with blood bank for DTT-treated crossmatching or use phenotype/genotype-matched RBCs.
Synonyms
Darzalex, Darzalex Faspro