Dinutuximab Brand Name– Unituxin
What is Dinutuximab
Dinutuximab is a chimeric monoclonal antibody (also known as ch 14.18), composed of a combination of mouse and human DNA, that works by binding to glycolipid disialoganglioside (GD2) on the cell surface of neuroblastoma cells and cells of neuroectodermal origin resulting in cell lysis through antibody-dependent cell-mediated and complement-dependent cytotoxicity.
Dinutuximab is indicated in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF; sargramostim), interleukin-2 (IL-2; aldesleukin), and 13-cis-retinoic acid (RA; isotretinoin) for the treatment of pediatric patients with high-risk neuroblastoma who achieved at least a partial response to prior first-line multiagent, multimodality therapy.
The 2-year event-free survival rate (primary endpoint) was significantly improved following immunotherapy with 6 cycles of isotretinoin plus 5 cycles of concomitant dinutuximab with alternating sargramostim and aldesleukin (66%) compared with standard therapy with 6 cycles of isotretinoin alone (46%; p = 0.01) in patients (median age, 3.8 years) with high-risk neuroblastoma who had a response to induction therapy and stem-cell transplantation in a randomized, phase III trial (n = 226; the Children’s Oncology Group (COG) ANBL0032 trial). The 2-year overall survival rate was also significantly improved with immunotherapy (86% vs 75%; p = 0.02).
Dinutuximab (Unituxin) was approved by the FDA in March 2015.
Indications
- neuroblastoma
For the treatment of high-risk neuroblastoma in patients who achieve at least a partial response to first-line multiagent, multimodality therapy in combination with 13-cis-retinoic acid (isotretinoin), granulocyte-macrophage colony-stimulating factor (sargramostim), and interleukin-2 (aldesleukin)
NOTE: Dinutuximab has been designated an orphan drug by the FDA for this indication.
Side Effects
- abdominal pain
- anaphylactoid reactions
- anemia
- angioedema
- anorexia
- antibody formation
- arthralgia
- back pain
- bleeding
- blurred vision
- bone pain
- bronchospasm
- capillary leak syndrome
- cardiac arrest
- chest pain (unspecified)
- diarrhea
- diplopia
- disseminated intravascular coagulation (DIC)
- dyspnea
- edema
- elevated hepatic enzymes
- epistaxis
- fever
- GI bleeding
- headache
- hematemesis
- hematoma
- hematuria
- hemolytic-uremic syndrome
- hyperglycemia
- hypertension
- hypertriglyceridemia
- hypoalbuminemia
- hypocalcemia
- hypokalemia
- hypomagnesemia
- hyponatremia
- hypophosphatemia
- hypotension
- hypoxia
- infection
- infusion-related reactions
- lethargy
- leukoencephalopathy
- lymphopenia
- musculoskeletal pain
- myalgia
- mydriasis
- myelitis
- nasal congestion
- nausea
- neuropathic pain
- neurotoxicity
- neutropenia
- papilledema
- paresthesias
- peripheral neuropathy
- photophobia
- proteinuria
- ptosis
- seizures
- SIADH
- sinus tachycardia
- thrombocytopenia
- urinary incontinence
- urinary retention
- urticaria
- vomiting
- weakness
- weight gain
- wheezing
Monitoring Parameters
- arterial blood gases (ABGs)
- CBC with differential
- LFTs
- neurologic function
- ophthalmologic exam
- serum creatinine/BUN
- serum electrolytes
Contraindications
- anemia
- breast-feeding
- capillary leak syndrome
- contraception requirements
- electrolyte imbalance
- hemolytic-uremic syndrome
- hepatic disease
- hypocalcemia
- hypokalemia
- hyponatremia
- hypotension
- infection
- infusion-related reactions
- neuropathic pain
- neurotoxicity
- neutropenia
- ocular disease
- papilledema
- peripheral neuropathy
- pregnancy
- renal disease
- renal impairment
- reproductive risk
- respiratory insufficiency
- sepsis
- thrombocytopenia
- urinary retention
- visual disturbance
Interactions
- Clozapine
- Palifermin
- Penicillamine
- Tuberculin Purified Protein Derivative, PPD
