Persistent immune-related adverse events after cessation of checkpoint inhibitor therapy: Prevalence and impact on patients' health-related quality of life.

BACKGROUND

Immune checkpoint inhibitors (ICIs) may induce persistent immune-related adverse events (irAEs). We investigated persistent irAEs and implications on patients' lives compared to non-ICI-induced autoimmune diseases (AIs).

METHODS

The multicentre, cross-sectional study comprised 200 patients with cancer ≥12 weeks after ICI cessation (ICI-patients) and 2705 patients with AIs (AI-patients), recruited in German outpatient clinics and support groups. The prevalence of persistent irAEs subdivided in long-term (12 weeks to <12 months) and chronic irAEs (≥12 months) since ICI discontinuation, health-related quality of life (HRQoL) using the EuroQol 5D-5L (EQ-Index/VAS score), and burden of autoimmune symptoms and respective therapies were assessed.

RESULTS

Long-term/chronic irAEs occurred in 51.9%/35.5% of outpatient ICI-patients, including arthralgia (16.7%/16.1%), myalgia (13.0%/14.0%), hypothyroidism (11.1%/10.8%), xerostomia (7.4%/8.6%), vitiligo (13.0%/7.5%) and hypophysitis (9.3%/7.5%). ICI-patients with long-term/chronic irAEs reported clinically significantly reduced HRQoL compared to ICI-patients without long-term/chronic irAEs (EQ-Index score: 0.767/0.752 versus 0.920/0.923, p < 0.001/0.001; EQ-VAS score: 52.2/52.0 versus 63.6/74.7, p =/< 0.040/0.001). Multiple linear regression analyses confirmed clinically significant reductions in HRQoL scores by chronic irAEs (EQ-Index/VAS score: -0.163/-23.4, p < 0.001/0.001). HRQoL, burden of autoimmune symptoms and burden of respective therapies in ICI-patients with chronic irAEs were similar to AI-patients with non-exacerbated AIs. Patients with chronic irAEs felt inadequately informed about side-effects compared to patients without chronic irAEs (p < 0.001).

CONCLUSION

Persistent irAEs impose a significant burden on patients after ICI cessation. Especially in early tumour stages, risk-benefit ratios must be carefully evaluated, and patients need to be informed about potential long-term sequelae.

Informations de copyright

Copyright © 2022 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S. Zierold has received speaker fees and/or travel grants from BMS, Sun Pharma and MSD. M. M. Sachse reports speaker honoraria from Novartis and advisory board honoraria from Sanofi Genzyme. D. Tomsitz reports consultancy, speaker fees and/or travel grants from BMS, Roche, Novartis, Sanofi, Recordati, Kyowa Kirin and Sun Pharma. K. Schilbach has served as consultant and/or has received honoraria from Recordati rare diseases, Pfizer, Ipsen, Sandoz and Consilient Health. There are no conflicts of interest concerning the present study. K. C. Kähler has served as consultant and/or has received honoraria from Amgen, Roche, Bristol Myers Squibb, Merck Sharp and Dohme, Pierre Fabre and Novartis; travel support from Amgen, Merck Sharp and Dohme, Bristol Myers Squibb, Amgen, Pierre Fabre, Medac and Novartis. L. E. French has served as paid consultant and/or speaker for Galderma, Janssen, Leo Pharma, Eli Lilly, Almirall, Union Therapeutics, Regeneron, Novartis, Amgen, Abbvie, UCB, Biotest, AC-Immune and InflaRx. None of these activities pertain to cancer immunotherapy and ICIs however. L. Heinzerling reports consultancy, speaker fees, travel grants and/or research funding: BMS, MSD, Merck, Roche, Amgen, Curevac, Novartis, Sanofi and Pierre Fabre; clinical studies: BMS, MSD, Merck, Roche, Amgen, GSK, Curevac and Novartis. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.