Darzalex

Newly diagnosed multiple myeloma (in combination with various regimens including bortezomib/melphalan/prednisone, lenalidomide/dexamethasone, or bortezomib/thalidomide/dexamethasone); Relapsed/refractory multiple myeloma (in various combinations or as monotherapy after ≥3 prior lines); Light chain (AL) amyloidosis

IV dosing (varies by regimen): 16 mg/kg weekly (weeks 1-8), q2w (weeks 9-24), then q4w until progression
Subcutaneous (Faspro): 1800 mg fixed dose SC over ~3-5 minutes with same schedule
Pre-medications: Corticosteroid, antipyretic, antihistamine 1-3 hours pre-infusion; post-infusion corticosteroid

Injection: 20 mg/mL in 5 mL (100 mg) and 20 mL (400 mg) single-dose vials; Darzalex Faspro (subcutaneous): 1800 mg/30,000 units co-formulated with hyaluronidase

Refer to the complete prescribing information for contraindications. Darzalex prescribing should account for patient-specific factors including hypersensitivity to the active ingredient or any excipients.

• Infusion-Related Reactions: Occurred in ~40% of patients (IV), mostly Grade 1-2. Pre-medicate and monitor.
• Interference with Blood Typing: Daratumumab binds CD38 on red blood cells, causing positive indirect Coombs test. Type and screen before starting.
• Neutropenia/Thrombocytopenia: Monitor CBCs periodically.
• Embryo-Fetal Toxicity

Infusion reactions (40% IV, 11% SC), fatigue (26%), nausea (22%), diarrhea (17%), upper respiratory infection (20%), muscle spasms (13%), cough (15%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Consult the complete prescribing information for drug interactions, including effects on CYP enzymes, transporters, and concomitant medications that may require dose adjustments or monitoring.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Daratumumab is a human IgG1κ monoclonal antibody that binds to CD38, a transmembrane glycoprotein highly expressed on multiple myeloma cells. It induces tumor cell death through complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis, and direct apoptosis via Fc-mediated cross-linking.

Half-life: approximately 18 ± 9 days. Clearance: 171 ± 81 mL/day. Vd: 4.7 ± 1.3 L. Steady-state reached by approximately 5 months of weekly dosing. Linear PK at doses ≥1 mg/kg.

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• CASTOR — Daratumumab + bortezomib/dex vs. bortezomib/dex in relapsed MM. Phase III, n=498.
  🔬 NCT02136134 ↗ 📄 Primary Publication ↗
• POLLUX — Daratumumab + lenalidomide/dex vs. lenalidomide/dex in relapsed MM. Phase III, n=569.
  🔬 NCT02076009 ↗ 📄 Primary Publication ↗

Darzalex has FDA-approved indications across the following cancer types covered on PipelineEvidence: