Dinutuximab
Indications
Dinutuximab is used for:
Neuroblastoma of pediatric patients
Adult Dose
Child Dose
Injection
Neuroblastoma
Indicated in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA) for pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-time multiagent, multimodality therapy
17.5 mg/m²/day IV over 10-20 hr for 4 consecutive days for maximum of 5 cycles
Cycles 1, 3, and 5 (24 days' duration): Administer dinutuximab on days 4, 5, 6, and 7
Cycles 2 and 4 (32 days' duration): Administer dinutuximab on days 8, 9, 10, and 11
Initiate at infusion rate of 0.875 mg/m²/hr for 30 min; may gradually increase infusion rate, as tolerated, to maximum of 1.75 mg/m²/hr
Renal Dose
Administration
IV Preparation
Inspect visually for particulate matter and discoloration prior to administration
Discard the vial if the solution is cloudy, has pronounced discoloration, or contains particulate matter
Aseptically withdraw the required volume of dinutuximab from the single-use vial and inject into a 100 mL bag of 0.9% NaCl injection, USP
Mix by gentle inversion; do NOT shake
Contra Indications
Hypersensitivity
Precautions
Neurological Disorders of the Eye: Interrupt Unituxin for dilated pupil with sluggish light reflex or other visual disturbances and permanently discontinue Unituxin for recurrent eye disorders or loss of vision. (
Prolonged Urinary Retention and Transverse Myelitis: Permanently discontinue Unituxin and institute supportive care.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Permanently discontinue Unituxin and institute supportive care for signs and symptoms of RPLS.
Capillary leak syndrome and hypotension: Administer required prehydration and monitor patients closely during treatment. Depending upon severity, manage by interruption, infusion rate reduction, or permanent discontinuation.
Infection: Interrupt until resolution of systemic infection.
Bone marrow suppression: Monitor peripheral blood counts during Unituxin therapy.
Electrolyte abnormalities: Monitor serum electrolytes closely.
Atypical hemolytic uremic syndrome: Permanently discontinue Unituxin and institute supportive management.
Embryo-Fetal toxicity: May cause fetal harm. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception.
Pregnancy-Lactation
Pregnancy
Studies in pregnant women and reproductive studies in animals have not been performed; monoclonal antibodies are transported across placenta in a linear fashion as pregnancy progresses, with the largest amount transferred during the third trimester; advise pregnant women of potential risk to a fetus; advise females of reproductive potential to use effective contraception during treatment and for 2 months after the last dose of dinutuximab
Lactation
Unknown whether distributed in breast milk; potential for serious adverse reactions in a breastfed infant; advise nursing mother to discontinue breastfeeding during therapy
Interactions
Adverse Effects
Side effects of Dinutuximab :
>10% (All Grades)
Dinutuximab/retinoic acid group
Pain (85%)
Pyrexia (72%)
Edema (17%)
Thrombocytopenia (66%)
Lymphopenia (62%)
Anemia (51%)
Neutropenia (39%)
Hypotension (60%)
Capillary leak syndrome (40%)
Hemorrhage (17%)
Hypertension (14%)
Hyponatremia (58%)
Hypokalemia (43%)
Hypoalbuminemia (33%)
Hypocalcemia (27%)
Hypophosphatemia (20%)
Hyperglycemia (18%)
Hypertriglyceridemia (16%)
Decreased appetite (15%)
Hypomagnesemia (12%)
Increased alanine aminotransferase (56%)
Increased aspartate aminotransferase (28%)
Increased serum creatinine (15%)
Increased weight (10%)
Vomiting (46%)
Diarrhea (43%)
Nausea (10%)
Urticaria (37%)
Hypoxia (24%)
Tachycardia (19%)
Sepsis (18%)
Device-related infection (16%)
Proteinuria (16%)
Peripheral neuropathy (13%)
Mechanism of Action
Chimetic monoclonal antibody that binds to the glycolipid disialoganglioside (GD2). GD2 is a glycolipid expressed on neuroblastoma cells and on normal cells of neuroectodermal origin, including central nervous system and peripheral nerves
Dinutuximab binds to cell surface GD2 and induces lysis of GD2-expressing cells through antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity