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Recurrence of Immune-Related Adverse Events After Checkpoint Inhibitor Rechallenge in Patients With Cancer


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A study reported in JAMA Oncology by Dolladille et al using pharmacovigilance data from the World Health Organization database VigiBase found that the same immune-related adverse events (irAEs) associated with discontinuation of immune checkpoint inhibitor therapy recurred in 28.8% of patients rechallenged with the same immune checkpoint inhibitor.

Study Details

The analysis included a total of 24,079 irAE cases associated with at least one immune checkpoint inhibitor. Among the 24,079 irAE cases, 6,123 (25.4%) were associated with an immune checkpoint inhibitor rechallenge. Analysis included risk of recurrence among informative rechallenges, defined as those with known irAE recurrence status.

KEY POINTS

  • Among the 6,123 irAEs associated with immune checkpoint inhibitor rechallenge, 452 (7.4%) were informative rechallenges.
  • Among the 452 informative rechallenges, recurrence of the initial irAE was observed in 130 cases (28.8%).
  • In univariate analysis, colitis, hepatitis, and pneumonitis were associated with increased recurrence rates. Adrenal events were associated with lower recurrence rates.

Key Findings

Among the 6,123 irAEs associated with immune checkpoint inhibitor rechallenge, 452 (7.4%) were informative rechallenges. Among the 452 informative rechallenges, recurrence of the initial irAE was observed in 130 cases (28.8%).

In univariate analysis, colitis (reporting odds ratio [OR] = 1.77, P = .01), hepatitis (reporting OR = 3.38, P = .01), and pneumonitis (reporting OR = 2.26, P = .01) were associated with increased recurrence rates. Adrenal events were associated with lower recurrence rates (reporting OR = 0.33, P = .03) compared with other irAEs.

In multivariate analysis adjusting for age, sex, immune checkpoint inhibitor regimen, follow-up status, and irAE types, factors associated with significantly higher risk of irAE recurrence were:

  • Use of an anti–cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) regimen (reporting OR = 3.5, P = .04)
  • Colitis (reporting OR = 2.99, P < .001)
  • Hepatitis (reporting OR = 3.38, P = .01)
  • Pneumonitis (reporting OR = 2.26,  P = .01).

The investigators concluded, “This cohort study found a 28.8% recurrence rate of the same irAE associated with the discontinuation of immune checkpoint inhibitor therapy after a rechallenge with the same immune checkpoint inhibitor. Resuming immune checkpoint inhibitor therapy could be considered for select patients, with appropriate monitoring and use of standard treatment algorithms to identify and treat toxic effects.”

Charles Dolladille, MD, MSc, of Normandie University, UNICAEN, CHU de Caen Normandie, Caen, is the corresponding author for the JAMA Oncology article.  

Disclosure: This study was funded by CHU Caen Normandie and Université de Caen Normandie. For full disclosures of the study authors, visit jamanetwork.com.


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