Daratumumab Indications
Daratumumab is a CD38-targeting monoclonal antibody used for the treatment of multiple myeloma, both in newly diagnosed patients and in relapsed/refractory disease, administered as monotherapy or in combination with standard regimens.
Primary Indications
Relapsed/Refractory Multiple Myeloma
Daratumumab is FDA-approved for relapsed/refractory multiple myeloma in patients who have received at least 3 previous therapies including proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs), or who have disease that is double refractory to a PI/IMiD combination 1.
Preferred Combination Regimens for Relapsed Disease
Daratumumab/lenalidomide/dexamethasone (DRd) is the preferred first-line option for first relapse, producing an 85% overall response rate versus 63% with lenalidomide/dexamethasone alone, with a 69% reduction in risk of disease progression or death (median PFS 16.7 vs 7.1 months) 2.
Daratumumab/bortezomib/dexamethasone (DVd) is the preferred option for lenalidomide-refractory disease, achieving an 82.9% overall response rate versus 63.2% with bortezomib/dexamethasone alone, with particularly strong benefit in patients with only one prior line of therapy (median PFS 27.0 vs 7.9 months) 2.
Daratumumab/pomalidomide/dexamethasone (DPd) is recommended for patients refractory to both lenalidomide and bortezomib 2.
Daratumumab monotherapy achieves approximately 30-42% overall response rates in heavily pretreated patients, with rapid, deep, and durable responses even in patients with minimal response or stable disease showing overall survival benefit 3, 4.
Newly Diagnosed Multiple Myeloma
Transplant-Ineligible Patients
Daratumumab/lenalidomide/dexamethasone (DRd) is a Category 1 preferred option, demonstrating unprecedented efficacy in the MAIA trial with median treatment duration of 25.3 months 1.
Daratumumab/bortezomib/melphalan/prednisone (DVMP) showed superior outcomes versus VMP alone in the ALCYONE trial for transplant-ineligible patients 5.
Transplant-Eligible Patients
Daratumumab/bortezomib/thalidomide/dexamethasone (Dara-VTd) significantly improves stringent complete response rates and progression-free survival compared with VTD alone in the CASSIOPEIA trial 5.
Daratumumab/bortezomib/lenalidomide/dexamethasone (Dara-VRD) achieves significantly higher stringent complete response rates in the GRIFFIN trial 5.
Mechanism of Action
Daratumumab kills myeloma cells through multiple mechanisms: antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), antibody-dependent cellular phagocytosis (ADCP), direct apoptosis, and immunomodulation by interfering with CD38 enzyme activity 2, 5.
Administration Formulations
Intravenous formulation: Initial infusions take approximately 4.2 hours, with subsequent infusions averaging 3.4 hours 1.
Subcutaneous formulation: Administration time reduced to median 5 minutes, with comparable clinical activity to IV formulation and lower infusion-related reaction rates (≤9.0%) 6, 4.
Common Pitfalls and Important Considerations
Infusion-related reactions occur in 42-45% of patients (predominantly Grade 1-2), with 92% limited to the first infusion 7, 1. Pre-medicate with antihistamines, antipyretics, and corticosteroids, and administer post-infusion oral corticosteroids to reduce delayed reactions 1.
Daratumumab interferes with blood bank testing by binding to CD38 on red blood cells, causing positive indirect Coombs tests that may persist for 6 months 2, 1. Perform comprehensive red cell antigen screening before initiating therapy 2.
Daratumumab interferes with serum protein electrophoresis and immunofixation in patients with IgG kappa myeloma, potentially impacting complete response determination 1. Mass spectrometry can reliably distinguish daratumumab from patient M-protein 2.
Monitor complete blood counts regularly: thrombocytopenia occurs in 45-54%, neutropenia in 12.8%, and anemia in 14-33% of patients 7, 1. Consider withholding treatment until recovery of blood counts 1.
Herpes zoster prophylaxis is required due to increased upper respiratory tract infections and reactivation risk 7.
Patients with chronic obstructive pulmonary disease require additional post-infusion medications, including short- and long-acting bronchodilators and inhaled corticosteroids 1.