Safety of Infusing Ipilimumab Over 30 Minutes

Abstract

Purpose: The approved dose of ipilimumab is 3 mg/kg infused over 90 minutes; however, in clinical trials, 10 mg/kg has also been infused over 90 minutes. At this higher dose, patients receive 3 mg/kg within the first 27 minutes of treatment. We sought to determine whether the standard dose of 3 mg/kg could be safely infused over 30 minutes.

Methods: We reviewed retrospectively the incidence of infusion-related reactions (IRRs) to ipilimumab at our institution in patients receiving doses of either 3 or 10 mg/kg infused over 90 minutes. Our findings led to a change in institutional guidelines for ipilimumab infusion time from 90 minutes to 30 minutes. We reviewed the first 14 months of our prospective experience using a 30-minute infusion of ipilimumab.

Results: Between April 1, 2008, and June 30, 2013, 595 patients received 2,507 doses of ipilimumab infused at either 3 mg/kg (n = 457) or 10 mg/kg (n = 138) over 90 minutes. Although the 10 mg/kg group had a higher incidence of IRRs (4.3%) than the 3 mg/kg group (2.2%), this difference was not statistically significant (P = .22). In 120 patients treated prospectively with ipilimumab 3 mg/kg infused over 30 minutes, seven patients (5.8%) had an IRR (P = .06 compared with 90-minute infusions). All IRRs occurred at dose 2; six were grade 2, and one was grade 3. All seven patients received subsequent doses of ipilimumab safely, the majority with premedication.

Conclusion: Ipilimumab at 3 mg/kg can be infused safely over 30 minutes with an acceptably low incidence of IRRs. After an IRR, patients can safely receive additional doses of ipilimumab with premedication.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

© 2015 by American Society of Clinical Oncology.

Figures

Fig 1.

Incidence of infusion-related reactions with 90-minute infusions. Patients received either 3 mg/kg (457 patients) or 10 mg/kg (138 patients). Stacked bar graphs indicate patients who did not have an infusion reaction (gold bars) and those who did have a reaction (blue bars). Infusion reactions were seen in 10 patients (2.2%) and six patients (4.3%) at the 3 and 10 mg/kg doses, respectively (P = .22, Fisher's exact test).

Fig 2.

Initial infusion reactions according to dose and treatment number. Infusion reactions that occurred with the first, second, third, fourth, and fifth or greater infusions in patients treated at 3 mg/kg (blue bars) and 10 mg/kg (gold bars) are shown. For patients who had infusion reactions during subsequent ipilimumab doses, only the first infusion reaction in each patient is indicated.