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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
  1. Léo Plaçais1,
  2. Stéphane Dalle2,
  3. Olivier Dereure3,
  4. Sabiha Trabelsi4,
  5. Sophie Dalac5,
  6. Delphine Legoupil6,
  7. Henri Montaudié7,
  8. Jean-Philippe Arnault8,
  9. Julie De Quatrebarbes9,
  10. Philippe Saiag10,
  11. Florence Brunet-Possenti11,
  12. Thierry Lesimple12,
  13. Eve Maubec13,
  14. François Aubin14,
  15. Florence Granel-Brocard15,
  16. Jean-Jacques Grob16,
  17. Pierre-Emmanuel Stoebner17,
  18. Clara Allayous18,
  19. Bastien Oriano18,
  20. Caroline Dutriaux19,
  21. Laurent Mortier20,
  22. Céleste Lebbe21
  1. 1 Internal Medicine and Clinical Immunology, Hopital Bicêtre, Le Kremlin-Bicêtre, Île-de-France, France
  2. 2 Dermatology, Centre Hospitalier Universitaire de Lyon, Lyon, Rhône-Alpes, France
  3. 3 Dermatology, CHU Montpellier, Montpellier, Languedoc-Roussillon, France
  4. 4 Dermatology, CHU Grenoble Alpes, Grenoble, Auvergne-Rhone-Alpes, France
  5. 5 Dermatology, CHU Dijon, Dijon, Bourgogne, France
  6. 6 Dermatology, CHU Brest, Brest, Bretagne, France
  7. 7 Dermatology, University Hospital, Nice, France
  8. 8 Dermatology, Centre Hospitalier Universitaire Amiens-Picardie, Amiens, Hauts-de-France, France
  9. 9 Dermatology, Centre Hospitalier Annecy Genevois, Epagny Metz-Tessy, France
  10. 10 Dermatology, Hôpital Ambroise Paré, Neuilly-sur-Seine, Île-de-France, France
  11. 11 Oncodermatology, Hopital Bichat - Claude-Bernard, Paris, France
  12. 12 Oncology, Centre Eugene Marquis, Rennes, France
  13. 13 Dermatology, Hopital Avicenne, Bobigny, France
  14. 14 Dermatology, CHU Besancon, Besancon, France
  15. 15 Dermatology, CHU de Nancy, Nancy, Lorraine, France
  16. 16 Dermatology, Hôpital de la Timone, Marseille, Provence-Alpes-Côte d'Azu, France
  17. 17 Dermatology, CHU Nimes, Nimes, Languedoc-Roussillon, France
  18. 18 Dermatology, CHU Saint-Louis, Paris, Île-de-France, France
  19. 19 Dermatology, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, Aquitaine, France
  20. 20 Dermatology, CHU Lille, Lille, Hauts-de-France, France
  21. 21 Dermatology, Hopital Saint-Louis, Paris, Île-de-France, France
  1. Correspondence to Dr Léo Plaçais, Médecine Interne, Hospital Bicetre, Le Kremlin-Bicetre 94270, France; leoplacais{at}


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.

  • autoimmunity
  • immune system diseases
  • therapeutics

Data availability statement

Data will be available on request and acceptance of the MelBase cohort scientific board.

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Data availability statement

Data will be available on request and acceptance of the MelBase cohort scientific board.

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  • Handling editor Josef S Smolen

  • Contributors LP, CA, BO and CL had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. LP accepts full responsibility for the work and/or the conduct of the study, had access to the data and controlled the decision to punblish. Concept and design: LP, CA, BO, CL. Acquisition, analysis or interpretation of data: LP, SDalle, OD, ST, SDalac, DL, HM, J-PA, JDQ, PS, FB-P, TL, EM, FA, FG-B, J-JG, P-ES, CA, BO, CD, LM, CL. Drafting of the manuscript: LP, CA, BO, CL. Critical revision of the manuscript for important intellectual content: LP, SDalle, OD, ST, SDalac, DL, HM, J-PA, JDQ, PS, FB-P, TL, EM, FA, FG-B, J-JG, P-ES, CA, BO, CD, LM, CL. Statistical analysis: BO, CA, LP. Administrative, technical or material support: CA, CL. Supervision: LP, SDalle, OD, ST, SDalac, DL, HM, J-PA, JDQ, PS, FB-P, TL, EM, FA, FG-B, J-JG, P-ES, CA, BO, CD, LM, CL.

  • Funding This study did not receive external funding, but the MelBase cohort is sponsored by the French National Cancer Institute and by BMS, MSD, Novartis and Roche.

  • Competing interests DL: fees from Novartis, BMS et MSD. PS: consulting fees from Roche, Novartis, BMS, Pierre FABRE, MSD. FB-P: consulting fees from BMS and Sanofi. TL: consulting fees from MSD, BMS, Pierre Fabre, Novartis. J-JG : consulting fees from MSD, Roche, Novartis, Amgen, Pierre-Fabre, Sanofi, Philogen, Merck, Pfizer. CA: grants from Amgen, BMS, Roche. LM: grants from BMS, Novartis, Roche, MSD, GSK, Pierre Fabre and consulting fees from BMS, Novartis, Roche, MSD, GSK, Pierre Fabre. CL: grants from BMS, MSD, Novartis, Sanofi, Pierre Fabre; consulting fees from BMS, MSD, Novartis, Amgen, Roche, Merck, Serono, Sanofi, Pierre Fabre and teaching fees from Roche, BMS, Novartis, Amgen, MSD.

  • Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.