Incidence of Olaratumab Infusion-Related Reactions
In a study reported in the Journal of Oncology Practice, Van Tine et al found that infusion-related reactions occurred in 14.4% of patients receiving olaratumab in clinical trials, with grade ≥ 3 events occurring in 2.3%. (Olaratumab was withdrawn from the global market on April 25, 2019, based on results from the ANNOUNCE trial, but patients may still receive the treatment through a continued access program).
Study Details
The study involved data from 485 patients in nine olaratumab clinical trials that were completed as of November 2016. Blood samples were analyzed for preexisting immunoglobulin E anti–galactose-α-1,3-galactose (anti-α-Gal) antibodies, which have been associated with infusion-related reactions, in 425 patients.
Incidence of Infusion-Related Reactions
In the clinical trials, infusion-related reactions of any grade were identified in 70 (14.4%) of 485 patients. The most common symptoms included flushing, fever or chills, and dyspnea. In 68 (97.1%) of the 70 patients with infusion-related reactions, the first reaction occurred during the first two cycles of treatment. Grade ≥ 3 infusion-related reactions occurred in 11 patients (2.3%); all of these events occurred during the first infusion and usually within 15 minutes of the start of the infusion. One infusion-related reaction–related fatality (0.2%) occurred in a nonpremedicated patient with grade ≥ 3 cardiac comorbidities.
Premedication, recommended in product labeling, was at investigator discretion in earlier trials. Overall, 243 patients received premedication and 242 did not. Any-grade infusion-related reactions occurred during the first dose of olaratumab in 9.9% vs 10.3% of these patients. Of the 11 patients with grade ≥3 infusion-related reactions, 6 did not receive premedication.
Nine patients (2.1%) had detectable anti-α-Gal antibodies above the manufacturer-specified upper limit of normal; grade ≥ 3 infusion-related reactions occurred in seven of these patients. Overall, 6 (10.7%) of 56 patients enrolled in trials in Missouri, Tennessee, and North Carolina—states in US regions with a previously reported higher prevalence of anti–α-Gal antibodies—had a grade ≥3 infusion-related reaction.
Analysis of postmarketing reports through October 2017 indicated a rate of severe infusion-related reactions of 2.4%, with infusion-related reactions being consistent in nature and severity with those in clinical trials.
The investigators concluded, “Premedication with corticosteroids and antihistamines should occur in all patients before olaratumab infusion, as indicated in labels in the United States and the European Union. Patients receiving olaratumab should be monitored for infusion-related reactions in a setting where resuscitation equipment is available for [their] treatment.”
Brian A. Van Tine, MD, of Washington University in St. Louis, is the corresponding author for the Journal of Oncology Practice article.
Disclosure: The study was supported by Eli Lilly. For full disclosures of the study authors, visit jop.ascopubs.org.
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