Safety of immune checkpoint inhibitor rechallenge after discontinuation for grade ≥2 immune-related adverse events in patients with cancer

Abstract

BackgroundSafety of rechallenge of immune checkpoint inhibitor (ICI) after grade ≥2 immune-related adverse events (irAEs) leading to ICI discontinuation remains unclear.MethodsAll adverse drug reactions involving at least one ICI reported up to December 31, 2019 were extracted from the French pharmacovigilance database. Patients were included if they experienced at least one grade ≥2 irAE resulting in ICI discontinuation, with subsequent ICI rechallenge. The primary outcome was the recurrence of at least one grade ≥2 irAE in these patients after ICI rechallenge.ResultsWe included 180 patients: 61.1% were men (median age of 66 years), 43.9% had melanoma and 78.9% were receiving anti-programmed cell death 1. First ICI discontinuation was related to 191 irAEs. After ICI rechallenge, 38.9% of the patients experienced at least one grade ≥2 irAE. Among them, 70.0% experienced the same irAE, 25.7% a distinct irAE, and 4.3% both the same and a distinct irAE. Lower recurrence rates of irAEs were associated with rechallenge with the same ICI treatment (p=0.02) or first endocrine irAEs (p=0.003). Gastrointestinal irAEs were more likely to recur (p=0.007). The median duration from ICI discontinuation to rechallenge and the severity of the initial irAE did not predict recurrent irAEs after ICI rechallenge (p=0.53 and p=0.40, respectively).ConclusionsIn this study, 61.1% of the patients who discontinued ICI treatment for grade ≥2 irAEs experienced no recurrent grade ≥2 irAEs after ICI rechallenge. Although ICI rechallenge appears to be safe under close monitoring, it should always be discussed balancing usefulness of rechallenge, patient comorbidities and risk of recurrence of first irAE(s). Due to inherent bias associated with pharmacovigilance studies, further prospective studies are needed to assess risk factors that may influence patient outcomes after ICI rechallenge.

Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update

“…GI irAEs were more likely to recur; however, there was no correlation between the severity of initial and subsequent irAEs. 279…”

Immune Checkpoint Inhibitor-Associated Colitis: From Mechanism to Management

“…Among these recurrent irAEs, colitis showed significantly higher incidence than other irAEs (227). Nearly 20%-30% of patients would experience recurrent grade 3 CIC (195,233). In our analysis, 12.5% (4/32) of patients (36,43,50,54) were retreated with the same ICI therapy used before, one of which experienced the recurrence of grade 3 enterocolitis (54).…”

“…Gobbini et al (231) demonstrated that NSCLC patients discontinuing for irAEs had more prolonged survival than those discontinuing for disease progression. After ICI rechallenge, the recurrence rate of irAEs varied from 37% to 78% (227,(232)(233)(234). Among these recurrent irAEs, colitis showed significantly higher incidence than other irAEs (227).…”

Guillain-Barré Syndrome-Like Polyneuropathy Associated with Immune Checkpoint Inhibitors: A Systematic Review of 33 Cases

“…And the variables associated with a higher recurrence rate of irAEs were anti-CTLA-4 regimen, age, colitis, hepatitis, and pneumonia, in order [ 68 ]. In addition, the duration from ICI discontinuation to rechallenge, and the severity of the initial irAEs did not predict whether irAEs would reappear after rechallenge of ICIs [ 69 ]. However, no relevant literature has been reported on whether discontinuation due to ICI-related GBS can rechallenge the same or different ICIs again.…”