General Information

Unituxin (dinutuximab) is a chimeric monoclonal antibody.

Unituxin is specifically indicated for use in combination with granulocyte-macrophage colonystimulating factor (GM-CSF), interleukin-2 (IL-2) and 13-cis-retinoic acid (RA), for the treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy.

Unituxin is supplied as a solution for intravenous infusion. The recommended dose of Unituxin is 17.5 mg/m2 /day administered as an intravenous infusion over 10 to 20 hours for 4 consecutive days for a maximum of 5 cycles. Unituxin should be initiated at an infusion rate of 0.875 mg/m2 /hour for 30 minutes. The infusion rate can be gradually increased as tolerated to a maximum rate of 1.75 mg/m2 /hour. Follow dose modification instructions (see drug label) for adverse reactions.

Clinical Results

FDA Approval

The FDA approval of Unituxin was based on a randomized, open-label, multicenter trial of 226 pediatrics with high-risk neuroblastoma whose tumors shrunk or disappeared after treatment with multiple-drug chemotherapy and surgery followed by additional intensive chemotherapy and who subsequently received bone marrow transplantation support and radiation therapy. Subjects were randomly assigned to receive either an oral retinoid drug, isotretinoin (RA), or Unituxin in combination with interleukin-2 and granulocyte-macrophage colony-stimulating factor, which are thought to enhance the activity of Unituxin by stimulating the immune system, and RA. Three years after treatment, 63% of subjects receiving the Unituxin combination were alive and free of tumor growth or recurrence, compared to 46% of subjects treated with RA alone. In an updated analysis of survival, 73% of subjects who received the Unituxin combination were alive compared with 58% of those receiving RA alone.

Side Effects

Adverse effects associated with the use of Unituxin may include, but are not limited to, the following:

pain

pyrexia

thrombocytopenia

lymphopenia

infusion reactions

hypotension

hyponatremia

increased alanine aminotransferase

anemia

vomiting

diarrhea

hypokalemia

capillary leak syndrome

neutropenia

urticaria

hypoalbuminemia

increased aspartate aminotransferase

hypocalcemia

Unituxin carries a Boxed Warning alerting patients and health care professionals that Unituxin irritates nerve cells, causing severe pain that requires treatment with intravenous narcotics and can also cause nerve damage and life-threatening infusion reactions, including upper airway swelling, difficulty breathing, and low blood pressure, during or shortly following completion of the infusion. Unituxin may also cause other serious side effects including infections, eye problems, electrolyte abnormalities and bone marrow suppression.

Mechanism of Action

Unituxin (dinutuximab) binds to the glycolipid GD2. This glycolipid is expressed on neuroblastoma cells and on normal cells of neuroectodermal origin, including the central nervous system and peripheral nerves. Dinutuximab binds to cell surface GD2 and induces cell lysis of GD2 expressing cells through antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).