Daratumumab

Daratumumab may increase neutropenia and thrombocytopenia when used in combination with other chemotherapy agents for the treatment of multiple myeloma. Lymphopenia, neutropenia, thrombocytopenia, and anemia (including grade 3 and 4 toxicity) were commonly reported as treatment emergent adverse reactions in clinical trials. Monitor for signs/symptoms of infection and bleeding. Monitor complete blood counts periodically; may require delay of daratumumab infusion to allow for neutrophil and/or platelet recovery. Supportive care with growth factors and/or platelet transfusions may be necessary.

Severe infusion reactions may occur (including bronchospasm, hypoxia, dyspnea, hypertension, laryngeal edema, and pulmonary edema), mostly during the first infusion. Signs and symptoms include cough, throat irritation, and nasal congestion, as well as chills, vomiting, and nausea. Less commonly reported symptoms include wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, and hypotension. Infusion reactions were reported in approximately 50% of patients in clinical trials. Reactions may also be seen during subsequent infusions, and generally occur either during the infusion or within 4 hours of completion; some reactions occurred up to 48 hours after the infusion. Premedication with antihistamines, antipyretics, and corticosteroids is required; interrupt infusion for any reaction and manage as appropriate. Reduce the infusion rate for grade 1, 2, or 3 reaction; permanently discontinue therapy for grade 4 infusion reaction. Administer in a facility with immediate access to resuscitative measures (eg, glucocorticoids, epinephrine, bronchodilators, and/or oxygen). Administer oral corticosteroids to all patients after daratumumab infusion to reduce the risk of delayed infusion reactions. Also consider short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease; monitor closely. Disease-related concerns:

Daratumumab (a human IgG kappa monoclonal antibody) may be detected on serum protein electrophoresis and immunofixation assays which monitor for endogenous M-protein. Interference with these assays by daratumumab may affect the determination of complete response and disease progression in some patients with IgG kappa myeloma protein. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Other warnings/precautions:

Through binding to CD38 on red blood cells, daratumumab use may result in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated Coombs test positivity may persist for up to 6 months after the last infusion. In addition, daratumumab (bound to red blood cells) masks antibody detection to minor antigens in the patient's serum; ABO and Rh blood type determination are not affected. Notify blood transfusion centers and blood banks that a patient has received daratumumab, and type and screen patients prior to therapy initiation.