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  • 54 Prognostic value of T cell immunoscore estimated from transcriptomic data in patients with advanced malignancies treated with immune checkpoint inhibitors

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Regular and Young Investigator Award Abstracts
Biomarkers, Immune Monitoring and Novel Technologies
54 Prognostic value of T cell immunoscore estimated from transcriptomic data in patients with advanced malignancies treated with immune checkpoint inhibitors
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  1. Ahmad Tarhini1,
  2. Payman Ghasemi Saghand2,
  3. Aik Choon Tan1,
  4. James Chen2,
  5. Aakrosh Ratan3,
  6. Martin McCarter4,
  7. John Carpton5,
  8. Howard Colman6,
  9. Alexandra Ikeguchi7,
  10. Igor Puzanov8,
  11. Susanne Arnold9,
  12. Michelle Churchman10,
  13. Patrick Hwu1,
  14. Jose Conejo-Garcia1,
  15. William (Bill) Dalton10,
  16. George Weiner11 and
  17. Issam El Naqa1
  1. 1H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
  2. 2The Ohio State University, Columbus, OH, USA
  3. 3University of Virginia, Charlottesville, VA, USA
  4. 4University of Colorado Cancer Center, Aurora, CO, USA
  5. 5USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA
  6. 6Huntsman Cancer Institute, Salt Lake City, UT, USA
  7. 7Stephenson Cancer Center, Oklahoma City, OK, USA
  8. 8Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
  9. 9Markey Cancer Center, Lexington, KY, USA
  10. 10M2Gen, ORIEN, Tampa, FL, USA
  11. 11University of Iowa Holden Cancer Center, Iowa City, IA, USA

Abstract

Background Evidence supports the association between tumor-infiltrating lymphocytes with disease prognosis and response to immunotherapy. Here, we evaluated the prognostic value of an immunoscore reflecting CD3+ and CD8+ T cell density in patients with advanced malignancies treated with immune checkpoint inhibitors (ICIs).

Methods We utilized real-world clinical and transcriptomic data collected under the Total Cancer Care Protocol (NCT03977402) and Avatar® project within the Oncology Research Information Exchange Network (ORIEN) of 18 cancer centers to which all included subjects provided a written informed consent at their participating institutions. The immunoscore for each patient was calculated based on the estimated densities of tumor CD3+ and CD8+ T cells (Galon, 2020) utilizing CIBERSORTx and the LM22 gene signature matrix. Overall survival (OS) predictions were assessed using Harrell’s concordance index (C-index). Kaplan-Meier (KM) curves and the log-rank test were used to assess the immunoscore ability to stratify risk groups.

Results Patients (n=522) with 4 cancer types including melanoma (n=125), renal cell carcinoma (n=149), non-small cell lung cancer (n=128) and head and neck cancer (n=120) treated with 6 immune checkpoint inhibitor (ICI) regimens were included in this analysis. ICI regimens were nivolumab (n=219), pembrolizumab (n=202), ipilimumab+nivolumab (n=69), ipilimumab (n=30), avelumab (n=1) and cemiplimab (n=1). Table 1 summarizes the overall C-index and associated 95% CIs and log-rank p values for the entire cohort resulting from estimated immunocore categorizations. KM analyses of the entire cohort are displayed in figure 1. We compared the performance of the immunoscore as a prognostic biomarker in the 4 cancer types, with significant results seen only in the melanoma and head and neck cancer cohorts (table 2, figure 2).

Conclusions The CD3+, CD8+ T Cell immunocore estimated from transcriptomic data represents a prognostic biomarker for estimating overall survival in patients with metastatic melanoma and head and neck cancer treated with ICIs in a real-world setting and can be used as a reference in prognostic biomarker development. Integration with other biomarker candidates that may guide the choice of ICI regimen (anti-PD1 monotherapy versus combinations) is underway.

Acknowledgements We are grateful to the participating patients and their family members as well as all research staff supporting the conduct of the Total Cancer Care protocol.

Trial Registration NCT03977402

Ethics Approval We utilized real-world clinical and transcriptomic data collected under the Total Cancer Care Protocol (NCT03977402) and Avatar® project within the Oncology Research Information Exchange Network (ORIEN) of 18 cancer centers to which all included subjects provided an IRB-approved written informed consent at their participating institutions.

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Abstract 54 Table 1

Overall C-index and associated 95% Cls and log-rank

View this table:
Abstract 54 Table 2

Overall C-index and associated 95% Cls and log-rank

Abstract 54 Figure 1
Abstract 54 Figure 1

Kaplan-Meier analysis for the entire cohort

Abstract 54 Figure 2
Abstract 54 Figure 2

Cancer-specific Kaplan Meier plots

https://doi.org/10.1136/jitc-2022-SITC2022.0054

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