Table 2.

Preventive and Supportive Care for Management of Anticipated Toxicities Associated With Administration of Dinutuximab in Combination With GM-CSF, IL-2, and RA.^a

Drug and Indication	Dosing and Administration	Patient Monitoring
Morphine sulfate  Pain management	Loading dose of 50 μg/kg immediately prior to dinutuximab infusion; continuous/PCA morphine during infusion	Substitute with fentanyl or hydromorphone if patient is unable to tolerate morphine
Lidocaineb  Pain management	IV bolus at 2 mg/kg in 50 mL normal saline over 30 minutes prior to start of dinutuximab infusion Once dinutuximab started, IV push at 1 mg/kg/h and continue until 2 hours after completion	Discontinue if patient becomes dizzy or develops perioral numbness, or tinnitus attributable to lidocaine
Gabapentinc  Pain management	If needed, 10 mg/kg PO may be given when starting morphine premedication; dose may be subsequently increased (to max 60 mg/kg/d, max daily dose 3600 mg/d) as needed	Titrate as ordered and recommended per institution pharmacy guidelines
Hydroxyzine and diphenhydramined  Allergic reactions	0.5 to 1.0 mg/kg, max 50 mg, or diphenhydramine (0.5–1.0 mg/kg, max 50 mg) over 10 to 15 minutes, starting 20 minutes prior to dinutuximab infusion and continuing, as tolerated, every 4 to 6 hours until end of dinutuximab infusion	Careful patient monitoring is required, as this drug combination has the potential for increased side effects, such as drowsiness, hypotension, difficulty urinating, and tachycardia
Acetaminophen  Fever or pain	10 mg/kg, max 650 mg, IV or PO 20 minutes prior to dinutuximab infusion and every 4 hours as needed for fever; administer every 4 to 6 hours during IL-2 plus dinutuximab cycles
Ibuprofene  Fever or pain	5 to 10 mg/kg/dose; not to exceed every 6 hours; administered between acetaminophen doses for control of persistent fever	Discontinue if bleeding occurs, platelet count drops below 50 000/μL, or evidence of renal dysfunction occurs
Antibiotics	Broad-spectrum antibiotics are recommended for febrile patients; dinutuximab immunotherapy should be discontinued until infection has resolved; some centers recommend using prophylactic antibiotics for patients with bacteremia during previous cycle

Abbreviations: GM-CSF, granulocyte-macrophage colony-stimulating factor; IL-2, interleukin 2; IV, intravenous; max, maximum; PCA, patient-controlled analgesia; PO (per os), by mouth; RA, 13-cis-retinoic acid.

^aModified from the ANBL0032 Protocol (Children’s Oncology Group, 2013).

^bRarely used and should be given under direction of pediatric pain specialist.

^cIn general, institutions report starting gabapentin 3 days prior to start of dinutuximab infusion, although some may start 1 to 2 weeks prior depending on institutional and prescriber preferences.

^dMay be used in combination.

^eNot preferred.