Abstract
Purpose
Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of certain cancers but cause immune-related adverse events (irAEs). Gastrointestinal irAEs may necessitate extended periods of steroid use and the initiation of selective immunosuppressive therapy (SIT) which could theoretically counteract the effect of ICIs. In this study, we aim to explore the impact of immunosuppression use and duration on cancer progression and progression-free survival (PFS).
Methods
This is a single-center retrospective review exploring cancer outcomes in patients taking ICIs who developed gastrointestinal irAEs within 1 year of ICI initiation. Cancer outcome and progression free survival (PFS) were measured and compared by using IBM SPSS Statistics 26.
Results
Of the 116 patients included in this study, 69 received immunosuppression to treat irAEs. The occurrence of colitis and use of immunosuppression for colitis were associated with less cancer progression by later assessment (p < 0.05). Shorter durations of steroids with or without SIT for colitis were associated with less cancer progression within the study window than no immunosuppression (p < 0.05). Immunosuppression has no effect on PFS (p < 0.05).
Conclusion
Our study reported shorter duration of steroid treatment for colitis may be associated with less cancer progression. Though the use of immunosuppression was not found to impact PFS, this may be confounded by the presence of colitis, which is known to improve cancer outcomes and could mask any negative impact of immunosuppression on survival. It may be preferable to limit long-term immunosuppression in the treatment of immune-mediated colitis to minimize potential complications. Prospective studies are needed to clarify this relationship, and treatments that abrogate the need for immunosuppression in these patients such as fecal microbiota transplantation.
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Data availability
The data sets used and analyzed in this study are available from the corresponding author upon reasonable request.
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Medical editing of this paper was provided by Ashli Nguyen-Villarreal, Associate Scientific Editor, and Sarah Bronson, Scientific Editor, in the Research Medical Library at The University of Texas MD Anderson Cancer Center.
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YW, who was the senior author of this article, developed the study concept, designed the study, interpreted the results, ensured the preservation of data accuracy and integrity at all stages, agreed to be accountable for all aspects of the study, was in charge of the overall direction and planning of the study, and contributed to the writing of the manuscript, with input from all authors. WM and YC collected the data for the study and conducted and interpreted the results of the manuscript. MS. and SN drafted the manuscript. MS conducted the biostatistical analysis. All the authors critically revised the final version of the manuscript and approved the final manuscript.
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The ethics approval for this study was granted by the institutional review board at The University of Texas MD Anderson Cancer Center (PA18-0472). Patient consent was waived for this study.
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Shatila, M., Ma, W., Cui, Y. et al. Effects of immunosuppressive treatment on patient outcomes after immune checkpoint inhibitor-related gastrointestinal toxicity. J Cancer Res Clin Oncol 149, 7793–7803 (2023). https://doi.org/10.1007/s00432-023-04736-9
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DOI: https://doi.org/10.1007/s00432-023-04736-9