Immune checkpoint inhibitors (ICIs), despite being effective against tumors, have been linked to a wide range of immune-related adverse events (irAEs). As soon as an irAE of grade greater than equal to 2 or higher occurs, ICI must be stopped. Unfortunately, the decision to resume ICI medication is still difficult for many patients. Researchers performed a retrospective analysis of 1,051 adult patients with stage IV non-small cell lung cancer (NSCLC) treated with ICIs at a single institution between January 2015 and December 2020 and found that 99 (9.4%) patients experienced irAEs of grade greater 2 that required treatment cessation. About 40 patients participated in a second round of treatment (the rechallenged group), whereas 59 others gave up and stopped taking their medication (discontinued group).

Both groups’ patients were identical to one another at the outset. Rechallenged patients experienced milder irAEs at first. About 24 of 40  patients (60%) experienced a recurrence or new irAE after rechallenge. Twenty (50%) developed a second grade greater than equal to 2 irAEs. No irAE of grade 4 or irAE-related deaths occurred upon rechallenge. Multivariate analysis revealed no significant differences in overall survival (OS) (HR: 1.10, 95% CI: 0.57-2.15, P=.77) or progression free survival (PFS) (HR: 0.87, 95% CI: 0.45-1.71, P=.69) between the 2 groups, with the best objective response preceding the initial irAEs being the only variable affecting OS and PFS.

There was an increased probability of irAEs of grade 2 after a rechallenge. If the irAEs occurred initially and were resolved, the risk would decrease. Patients who underwent ICI rechallenge did not fare worse than those who did not in terms of overall survival. After experiencing irAEs of grade 2, particularly those of a severe nature, it is best to stop using ICI permanently.