Management of Adverse Effects in Daratumumab Therapy

Documented Adverse Effects

Infusion-related reactions occur predominantly with the first infusion (92% of reactions limited to first dose), with Grade 1-2 reactions in approximately 42-45% of patients, and Grade 3 reactions in 8.6% of patients, according to the National Comprehensive Cancer Network 1, 2, 3, 4
Thrombocytopenia occurs in 45-54% of patients in combination regimens, and neutropenia occurs in 12.8% of patients when combined with bortezomib, with an increased risk with lenalidomide combinations, as reported by the National Comprehensive Cancer Network 1, 4, 6, 7
Anemia occurs in 14-33% of patients depending on the regimen, according to the National Comprehensive Cancer Network 3, 4
Upper respiratory tract infections are increased with daratumumab-lenalidomide combinations, and herpes zoster reactivation risk requires prophylaxis, as recommended by the National Comprehensive Cancer Network 1, 7, 8
Fatigue occurs in 39.6% of patients, and nausea occurs in 29.2% of patients, according to the National Comprehensive Cancer Network 3
Peripheral neuropathy occurs in 47% of patients in the CASTOR trial, though primarily attributable to bortezomib, as reported by the Mayo Clinic Proceedings 1, 6

Dexamethasone-induced fluid retention is a common cause of edema in patients on daratumumab combinations, and lenalidomide-associated edema can also occur, as reported by the Mayo Clinic Proceedings 1, 6, 7
Carfilzomib-related cardiac effects, such as cardiac failure (3.8-4.8%) and hypertension, can cause edema, according to the National Comprehensive Cancer Network 4
Renal dysfunction from multiple myeloma, cardiac amyloidosis, and hypoalbuminemia are disease-related causes of edema, as reported by the National Comprehensive Cancer Network 3, 8
Unrelated medical conditions, such as venous thromboembolism, congestive heart failure, chronic venous insufficiency, and hepatic dysfunction, can also cause edema, according to the National Comprehensive Cancer Network and the Mayo Clinic Proceedings 8, 9

The National Comprehensive Cancer Network recommends investigating the underlying cause of edema rather than attributing it to daratumumab, and assessing combination therapy components, renal function, and screening for thrombosis 1, 8
The Mayo Clinic Proceedings suggests evaluating cardiac function with an echocardiogram if bilateral edema with dyspnea exists, particularly in patients receiving carfilzomib combinations 4, 5, 9
Standard edema management with diuretics, leg elevation, compression stockings, and sodium restriction is recommended as clinically appropriate, according to the National Comprehensive Cancer Network 8