Side Effects From Immune Checkpoint Inhibitors Vary by Regimen in Advanced Melanoma

By Reuters Staff

April 08, 2020

NEW YORK (Reuters Health) - Some immune-checkpoint inhibitor (ICI) regimens for advanced melanoma carry a lower risk of immune-related adverse events (irAEs) than others, according to a new systemic review and network meta-analysis.

"These findings suggest that for patients with advanced melanoma at high risk of irAEs, pembrolizumab, 2 mg/kg, every 3 weeks, nivolumab, 3 mg/kg, every 2 weeks, and pembrolizumab, 10 mg/kg, every 3 weeks may be the preferred treatment regimens (with respect to irAE risks) among the ICI regimens reported, whereas ipilimumab, 10 mg/kg, every 3 weeks alone and nivolumab, 1 mg/kg, every 3 weeks combined with ipilimumab, 3 mg/kg, every 3 weeks should be used with caution," Ching-Yuan Chang of the University of Florida College of Pharmacy, in Gainesville, and colleagues conclude in JAMA Network Open.

While ICIs extend survival in patients with advanced melanoma, they are associated with irAEs that can affect the skin, gastrointestinal tract, endocrine system, liver and lungs, Chang and her team note. Rates of irAEs in published randomized controlled trials in advanced melanoma patients range from 54% to 96%, they add.

"Without proper management, irAEs can be severe and life-threatening and may result in treatment discontinuation or failure," the authors write.

They analyzed nine randomized controlled trials of eight treatment regimens including more than 5,000 patients in total to estimate the likelihood of being associated with the lowest irAE risk for each regimen.

The three regimens most likely to carry the lowest risk of any irAE or severe irAE were pembrolizumab 2 mg/kg, every three weeks; nivolumab, 3 mg/kg, every two weeks; and pembrolizumab, 10 mg/kg, every three weeks.

Nivolumab, 3 mg/kg, every two weeks was the only regimen associated with a significantly lower risk of any irAEs compared with ipilimumab, 10 mg/kg, every three weeks, with an odds ratio of 0.34; this nivolumab regimen was also the only ICI treatment associated with a significantly lower risk of severe irAEs compared with chemotherapy.

Ipilimumab 10 mg/kg every three weeks and nivolumab 1 mg/kg every three weeks plus ipilimumab 3 mg/kg every three weeks each carried a higher risk of irAEs than the other ICI regimens.

The risk of irAEs with each ICI regimen also varied by affected organ system and severity.

"These findings provide additional evidence and insights for better clinical practice guidance on ICI use in terms of irAEs, especially in patients at high risk," Chang and colleagues write. "Specifically, for individuals with preexisting autoimmune diseases, initiating ICI regimens with a lower risk of any or severe irAEs is recommended to avoid irAEs. Also critical is regularly monitoring patients with advanced melanoma (eg, testing aspartate aminotransferase or alanine aminotransferase level every week) and then adjusting doses if needed."

The researchers report no funding or conflicts of interest.

SOURCE: JAMA Network Open, online March 25, 2020.