Quantifying the clinical severity of immune-related cutaneous adverse events in clinical trial patients: A prospective study using 3D-total body photography.

Abstract

e13548 Background: Accurate and comprehensive assessment of dermatologic adverse events (AEs) in clinical trials is challenging, given the heterogeneity of appearance and perception of these AEs. For dermatologic AEs, Common Terminology Criteria for Adverse Events (CTCAE) grading of clinical severity primarily relies on the clinician’s reporting of body surface area involved (BSA%) estimated by visual assessment combined with clinician’s interpretation of psychosocial impact, which can vary among raters. Although patient reported outcome (PRO-CTCAE) and QoL (SKINDEX-16) measures have been incorporated to improve accuracy and reliability of symptomatic AE evaluations, the subjective nature of dermatologic CTCAE grading remains. Clinical photography is routinely used to aid in visual comparison but cannot be incorporated to standardized measures due to inconsistencies in lighting, distance from the camera, and position. This prospective study aims to validate the accuracy and utility of affected BSA% using 3D-total body photography (TBP) and quantitative imaging analytics for standardized, objective assessment of immune-related cutaneous adverse events (ircAE) in clinical trials and/or prospective studies. Methods: Polarized and non-polarized TBPs (Canfield Vectra WB360) were acquired on two dermatology clinic visits 2-6 weeks apart (n = 8, to date). CTCAE, PRO-CTCAE, SKINDEX-16 were evaluated by one investigator for both visits. Image analysis including BSA% calculation was conducted using Vectra measurement software by an investigator blinded to clinical grades. Means and ranges for change in CTCAE, BSA%, and SKINDEX-16 were calculated. Results: To date, 29 patients with ircAE have been enrolled with 8 completing both visits. A greater improvement in affected BSA% (-1.9, -13.0, -20.1) and SKINDEX-16 (-8,-11.9,-19.5) were associated with a greater degree of clinical improvement measured by CTCAE (0 to -3). Widest range in the degree of change in BSA% (-24.4, -6.8) and SKINDEX-16 (-31,19) was observed in the group with intermediate change in CTCAE (-2 to -1, n = 5). Conclusions: Estimating affected BSA% via visual assessment is subject to human error and rely on memory or comparison with unstandardized photos to detect clinical improvement of dermatologic conditions. This poses a challenge particularly for cases with mild or moderate clinical improvement, demonstrated by the wide range in the degree of change for BSA% and SKINDEX-16. With consistent lighting, position, and objective measurements, 3D-TBP quantitative image analysis shows promise in reproducible, standardized monitoring and quantification of ircAE clinical severity. Furthermore, the quantitative nature of TBP measurement suggests its potential utility for correlation with underlying immunophenotyping correlative studies and clinical trials.