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.
- immune system diseases
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.
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