Analysis of the tumor microenvironment before and during treatment with the help of artificial intelligence (AI) may aid in predicting response to pembrolizumab in patients with rare cancers, according to findings of a study published in the Journal for ImmunoTherapy of Cancer.
“AI-based pathology has the potential to provide clinicians with useful information on both the tumor and its surrounding microenvironment, helping to guide personalized treatment decisions for patients receiving immunotherapy,” said lead study author Aung Naing, MD, Professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center.
Study Methods
The researchers analyzed 256 baseline and 248 on-treatment biopsies from patients with rare tumors (n = 84; 10 cohorts) in a phase II trial of pembrolizumab. They looked at intratumoral tumor-infiltrating lymphocyte density and tumor content on hematoxylin and eosin (H&E) stained slides with a deep learning–based Lunit SCOPE IO analyzer. Changes in intratumoral tumor-infiltrating lymphocyte density and tumor content, analyzed with multiplex immunofluorescence, were correlated with survival outcomes.
Key Findings
In patients with higher intratumoral tumor-infiltrating lymphocytes, a baseline rate of ≥ 60 cells/mm2 (hazard ratio [HR] = 0.49; 95% confidence interval [CI] = 0.25–0.99; P = .046), higher CD8-positive and CD8-positive PD-1–positive cells, and lower FoxP3-positive CD8-positive PD-1–positive T-cell density were all individually considered to be related to a favorable progression-free survival. However, the same trend was not seen in the overall cohort (HR = 0.62; 95% CI = 0.37–1.06; P = .082).
In paired biopsies, an on-treatment increase in intratumoral tumor-infiltrating lymphocytes was associated with a trend toward prolonged progression-free survival (HR = 0.64; 95% CI = 0.40–1.06; P = .084) and was significantly associated with an improvement in overall survival (HR = 0.55; 95% CI = 0.35–1.01; P = .037). An on-treatment increase in intratumoral tumor-infiltrating lymphocytes was also associated with a reduced spatial distance between CD8-positive immune and tumor cells.
Decreased tumor content during treatment with pembrolizumab was significantly associated with improved progression-free (HR = 0.51; P = .019) and overall survival (HR = 0.54; P = .042).
Both increased intratumor tumor-infiltrating lymphocytes with decreased tumor content was significantly associated with a prolonged progression-free (HR = 0.35; P = .009) and overall survival (HR = 0.36; P = .029). Patients with these signals had a median overall survival of 42 months vs 10 months without.
“While this AI-powered approach needs validation, this is an exciting step forward because it shows that meaningful insights can be extracted from routine pathology samples across a diverse group of rare cancers,” Dr. Naing said.
DISCLOSURES: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., provided the study drug and funded the study. This work was supported in part by Lunit, which provided AI analysis; the National Cancer Institute at the National Institutes of Health; UT MD Anderson institutional programs; and the National Center for Advancing Translational Sciences at the National Institutes of Health. For full disclosures of the study authors, visit jitc.bmj.com.
