Highly variable timing renders immunotherapy efficacy and toxicity impractical biomarkers of one another in clinical practice.

Autor:	von Itzstein MS; Department of Internal Medicine (Division of Hematology-Oncology), Dallas, TX, United States.; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, United States., Yang Y; Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX, United States., Wang Y; Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX, United States., Hsiehchen D; Department of Internal Medicine (Division of Hematology-Oncology), Dallas, TX, United States., Sheffield TY; Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX, United States., Fattah F; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, United States., Popat V; School of Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States., Ahmed M; School of Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States., Homsi J; Department of Internal Medicine (Division of Hematology-Oncology), Dallas, TX, United States.; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, United States., Dowell JE; Department of Internal Medicine (Division of Hematology-Oncology), Dallas, TX, United States.; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, United States., Rashdan S; Department of Internal Medicine (Division of Hematology-Oncology), Dallas, TX, United States.; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, United States., Lohrey J; Department of Internal Medicine (Division of Hematology-Oncology), Dallas, TX, United States.; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, United States., Hammers HJ; Department of Internal Medicine (Division of Hematology-Oncology), Dallas, TX, United States.; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, United States., Hughes RS; Department of Internal Medicine (Division of Hematology-Oncology), Dallas, TX, United States.; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, United States., Wang T; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, United States.; Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX, United States., Xie Y; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, United States.; Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX, United States., Gerber DE; Department of Internal Medicine (Division of Hematology-Oncology), Dallas, TX, United States.; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, United States.; Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Apr 16; Vol. 15, pp. 1351739. Date of Electronic Publication: 2024 Apr 16 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1351739
Abstrakt:	Background: A useful clinical biomarker requires not only association but also a consistent temporal relationship. For instance, chemotherapy-induced neutropenia and epidermal growth-factor inhibitor-related acneiform rash both occur within weeks of treatment initiation, thereby providing information prior to efficacy assessment. Although immune checkpoint inhibitor (ICI)-associated immune-related adverse events (irAE) have been associated with therapeutic benefit, irAE may have delayed and highly variable onset. To determine whether ICI efficacy and irAE could serve as clinically useful biomarkers for predicting each other, we determined the temporal relationship between initial efficacy assessment and irAE onset in a diverse population treated with ICI. Methods: Using two-sided Fisher exact and Cochran-Armitage tests, we determined the relative timing of initial efficacy assessment and irAE occurrence in a cohort of 155 ICI-treated patients (median age 68 years, 40% women). Results: Initial efficacy assessment was performed a median of 50 days [interquartile range (IQR) 39-59 days] after ICI initiation; median time to any irAE was 77 days (IQR 28-145 days) after ICI initiation. Median time to first irAE was 42 days (IQR 20-88 days). Overall, 58% of any irAE and 47% of first irAE occurred after initial efficacy assessment. For clinically significant (grade ≥2) irAE, 60% of any and 53% of first occurred after initial efficacy assessment. The likelihood of any future irAE did not differ according to response (45% for complete or partial response vs. 47% for other cases; P =1). In landmark analyses controlling for clinical and toxicity follow-up, patients demonstrating greater tumor shrinkage at initial efficacy assessment were more likely to develop future grade ≥2 ( P =0.05) and multi-organ ( P =0.02) irAE. Conclusions: In contrast to that seen with chemotherapy and molecularly targeted therapies, the temporal relationship between ICI efficacy and toxicity is complex and bidirectional. In practice, neither parameter can be routinely relied on as a clinical biomarker to predict the other. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 von Itzstein, Yang, Wang, Hsiehchen, Sheffield, Fattah, Popat, Ahmed, Homsi, Dowell, Rashdan, Lohrey, Hammers, Hughes, Wang, Xie and Gerber.)
Databáze:	MEDLINE
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