Table 4.

Dose Modification Guidance for Management of Capillary Leak Syndrome During Administration of Dinutuximab in Combination With GM-CSF, IL-2, and RA.^a

Grade 3b: Severe symptoms
Onset of symptoms	• Discontinue dinutuximab infusion and IL-2 or GM-CSF • Administer supportive measuresc
Symptoms resolve	• Resume dinutuximab infusion at 0.875 mg/m2/h • Resume IL-2 or GM-CSF the following day at 50% of starting dose until last dose of dinutuximab for that cycle
Subsequent cycles	• If 50% dose of IL-2 or GM-CSF is tolerated, start at this dose and infuse dinutuximab at 0.875 mg/m2/h. If tolerated, increase IL-2 or GM-CSF to full dose the next day • If 50% dose of IL-2 is not tolerated, substitute GM-CSF for IL-2 in remainder of cycles • If 50% dose of GM-CSF is not tolerated, administer dinutuximab alone for remainder of GM-CSF cycles quences
Grade 4: Life-threatening conse
Onset of symptoms	• Discontinue dinutuximab infusion and IL-2 or GM-CSF for that cycle • Administer supportive measuresc
Subsequent cycles	• If capillary leak syndrome occurred during an IL-2 cycle, substitute GM-CSF for IL-2 in remainder of cycles • If capillary leak syndrome occurred during a GM-CSF cycle, administer dinutuximab alone for remainder of GM-CSF cycles

^aData from Unituxin (dinutuximab) injection, for intravenous use [prescribing information] (United Therapeutics Corp., 2015).

^bGraded per Common Terminology Criteria for Adverse Events version 3.0.

^cSupportive measures for grade 3 or 4 symptoms refers to sections of the prescribing instructions describing use of premedication and containing the warning regarding risk of capillary leak syndrome with dinutuximab therapy. In these sections, recommendations include administration of oral metolazone or IV furosemide every 6 to 12 hours, supplemental O₂, respiratory support, and albumin replacement as required.