Risk of irAEs in patients with autoimmune diseases treated by immune checkpoint inhibitors for stage III or IV melanoma: results from a matched case-control study.

Abstract

OBJECTIVE:

To quantify the risk of immune-related adverse events (irAEs) in patients with pre-existing autoimmune disease (pAID) treated by immune checkpoint inhibitors (ICIs) for stage III or IV melanoma.

METHODS:

Case-control study performed on a French multicentric prospective cohort of patients with melanoma, matched for irAE risk factors and oncological staging. Risk of irAE was assessed by logistic regression.

RESULTS:

110 patients with pAID were included and matched with 330 controls, from March 2013 to October 2020. Over a median follow-up period of 7.2 months for cases and 6.9 months for controls, the ORs of developing all-grade and grade ≥3 irAEs among cases compared with controls were 1.91 (95% CI (1.56 to 2.27)) and 1.44 (95% CI (1.08 to 1.82)), respectively. Patients with pAID had an increased risk of multiple irAEs (OR 1.46, 95% CI (1.15 to 2.67)) and a shorter time to irAE onset. In contrast, there were no difference in irAE-related mortality nor in the rate of treatment discontinuation, and a landmark analysis revealed a better survival at 24 months among cases (p=0.02). Thirty per cent of cases experienced a pAID flare during follow-up, and baseline immunosuppression did not prevent irAE occurrence. Last, we report associations between the pAID clinical subsets and organ-specific irAEs.

CONCLUSION:

In our study, patients with pAID were at greater risk of all-grade, severe and multiple irAEs, yet had a better 24-month survival than controls. Thus, patients with pAID should be eligible for ICI therapy but benefit from a close monitoring for irAE occurrence, especially during the first months of therapy.

• Authors: Léo Plaçais, Stéphane Dalle, Olivier Dereure, Sabiha Trabelsi, Sophie Dalac, Delphine Legoupil, Henri Montaudié, Jean-Philippe Arnault, Julie De Quatrebarbes, Philippe Saiag, Florence Brunet-Possenti, Thierry Lesimple, Eve Maubec, François Aubin, Florence Granel-Brocard, Jean-Jacques Grob, Pierre-Emmanuel Stoebner, Clara Allayous, Bastien Oriano, Caroline Dutriaux, Laurent Mortier, Céleste Lebbe
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 81 Issue 10 Pg. 1445-1452 (10 2022) ISSN: 1468-2060 [Electronic] England
• PMID: 35788496 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Antineoplastic Agents, Immunological
• Immune Checkpoint Inhibitors

Topics

• Antineoplastic Agents, Immunological (adverse effects)
• Autoimmune Diseases (chemically induced, drug therapy)
• Case-Control Studies
• Humans
• Immune Checkpoint Inhibitors (adverse effects)
• Immune System Diseases
• Melanoma (drug therapy)
• Prospective Studies
• Retrospective Studies