Daratumumab Dosing and Treatment Regimens for Multiple Myeloma
Standard Dosing Schedule
Daratumumab is administered at 16 mg/kg intravenously with a split-dosing schedule: weekly for the first 8 weeks (or 6-9 weeks depending on combination), then every 2 weeks for 16 weeks, followed by every 4 weeks until disease progression or unacceptable toxicity. 1, 2
Preferred Regimens by Clinical Setting
First Relapse (Lenalidomide-Sensitive)
- Daratumumab/Lenalidomide/Dexamethasone (DRd) is the NCCN Category 1 preferred option 1, 2, 3
- Lenalidomide 25 mg orally days 1-21 of each 28-day cycle 1
- Dexamethasone 40 mg on days 1,8,15, and 22 (20 mg for patients ≥75 years) 1
- Produces median PFS of 16.7 months vs 7.1 months without daratumumab (69% reduction in progression risk) 1, 2, 3
- For patients with only one prior therapy, median PFS extends to 27.0 months vs 7.9 months (78% risk reduction) 1, 2, 3
First Relapse (Lenalidomide-Refractory)
- Daratumumab/Bortezomib/Dexamethasone (DVd) is the NCCN Category 1 preferred option 1, 2, 3
- Bortezomib 1.3 mg/m² subcutaneously on days 1,4,8, and 11 of each 21-day cycle for 8 cycles 1
- Dexamethasone 20 mg orally on days 1,2,4,5,8,9,11, and 12 1
- Daratumumab given weekly for first 3 cycles (days 1,8,15), then day 1 only for cycles 4-8, then every 4 weeks 1
- Achieves 82.9% overall response rate vs 63.2% without daratumumab 2, 3
Double-Refractory Disease (Lenalidomide + Bortezomib)
Newly Diagnosed Transplant-Ineligible
- Daratumumab/Bortezomib/Melphalan/Prednisone (D-VMP) is NCCN Category 1 3
- 18-month PFS rate of 71.6% vs 50.2% without daratumumab 3
Subcutaneous Formulation Alternative
Subcutaneous daratumumab (1800 mg fixed dose) provides equivalent efficacy to IV formulation with 5-minute administration time and lower infusion reaction rates (≤9% vs 42-48%). 4, 5
- Can be used with all standard combination regimens 4
- Maintains similar exposure-response relationships to IV formulation 6
Critical Safety Management
Infusion-Related Reactions
- Occur in 42-48% of patients, predominantly Grade 1-2 2, 3, 5
- 92% of reactions occur only with the first infusion 1, 2
- First IV infusion requires ~7 hours; subsequent infusions typically 3-4 hours 6, 5
- Premedication mandatory: antihistamines, antipyretics, corticosteroids 5
Infection Prophylaxis
- Herpes zoster prophylaxis is required due to increased reactivation risk 2
- Grade 3-4 infections occur in 23.1% with daratumumab combinations vs 14.7% without 3
- Monitor closely for upper respiratory tract infections 1, 2
Hematologic Toxicity
- Neutropenia: 51.9% with DRd vs 37.0% without daratumumab 1, 3
- Thrombocytopenia: 12.7-45.3% depending on combination 3
- Anemia: 12.4% 1
Laboratory Interference
- Daratumumab causes positive indirect Coombs tests that may persist 6 months, interfering with blood bank crossmatching 2, 5
- Type and screen patients before starting therapy 5
- Interferes with serum protein electrophoresis in IgG kappa myeloma patients 2
Dose Modifications
No dose adjustment is recommended based on renal function, hepatic function, age, sex, race, weight, or ECOG performance status. 6
- Patients with IgG myeloma have lower exposure but similar response rates—no adjustment needed 6
- Lower albumin levels reduce exposure but do not affect efficacy—no adjustment needed 6
Heavily Pretreated Patients (≥3 Prior Lines)
Daratumumab monotherapy at 16 mg/kg is FDA-approved for patients with ≥3 prior therapies including a PI and IMiD, or double-refractory disease. 1, 3