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Chronic Inflammation as Response Biomarker in Immune Checkpoint Inhibition for Cancer

This presentation discusses the role of chronic inflammation as a potential biomarker for predicting response to immune checkpoint inhibitors in cancer treatment.

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Chronic Inflammation as Response Biomarker in Immune Checkpoint Inhibition for Cancer

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  1. The Role of Chronic Inflammation as a Response Biomarker to Immune Checkpoint Inhibition in Cancer S91 Sherif M. El-Refai, PharmD, MBA University of Kentucky College of Pharmacy Twitter: #AMIA2017

  2. Disclosure • I have no relevant relationships with commercial interests to disclose. AMIA 2017 | amia.org

  3. Learning Objectives • After participating in this session the learner should be better able to: • Understand the need for a robust biomarker with the use of immune checkpoint inhibitors (ICI) • Improve clinical outcomes by identifying variables that may be potential predictive biomarkers AMIA 2017 | amia.org

  4. Current Status of ICI Overall Survival B A

  5. Immune Checkpoint Inhibitors (ICI) AMIA 2017 | amia.org

  6. PD-L1 Expression Alone Is Not Enough • PD-L1 overexpression associated with improved clinical outcomes • However, robust responses in patients with low levels of expression prevent PD-L1 from being an exclusionary predictive biomarker • 96% of PD-L1 (+) melanomas associated with high tumor infiltrating lymphocytes (TILs) • 22% of PD-L1 (-) melanomas associated with TILs Patel SP et al. Mol Cancer Ther, 14(4) April 2015 Taube JM et al. SciTransl Med. 4(127) Mar 2012

  7. Opportunity for Peripheral Biomarkers

  8. Opportunity for Peripheral Biomarkers Chen DS, et al. Immunity. 2013, 39:1-10.

  9. Evidence for Potential Peripheral Marker Fehrenbacher L et al. Lancet (387) April 2016

  10. Primary Observations Hypothesis: Other peripheral factors influence the response to nivolumab treatment in NSCLC patients • Retrospective analysis of 45 Nivolumab-treated NSCLC Patients • Cycles of Nivolumab therapy were used as surrogate for response • Approximately 20% achieved objective response (>6 cycles)

  11. Primary Observations Chronic inflammatory conditions = COPD, Hypertension, Hyperlipidemia, Diabetes or Obesity Conclusion: Patients with a history of chronic inflammatory comorbidities, stay on Nivolumab for a longer period of time.

  12. Outcomes Analysis – Overall Survival Health Outcomes Analysis Stratify by Chronic Inflammatory Condition, Propensity-score matching with CCI & Previous Therapies ICI-Treated Population (All Cancers) 24-Month Pre-Index Truven claims data stratification and analysis approach. An illustration representing the manner in which the desired patient population was identified under Truven and how the relationship between chronic inflammatory conditions and ICIs are assessed. 12-Months Post-Index Pre-Index • Observational cohort study (January 2013 – December 2015) • Objective response = one-year overall survival • ICI Coding • Nivolumab(C9453, J9299), Pembrolizumab(C9027, J9271), Ipilimumab (J9228)

  13. Propensity Score Matching Controlling Baseline Covariates Charlson Comorbidity Index (CCI) – 17 comorbid categories, Weighted Charlson ME et al. J Chronic Dis 1987

  14. Patient Demographics

  15. Assessing Balance Post-Matching

  16. Chronic Inflammation History Correlates with ICI Response Conclusion: Patients with a history of chronic inflammatory comorbidities, have improved one-year survival rates as compared to ICI-treated patients without a history of chronic inflammation.

  17. Limitations • Limitations of retrospective study • Population size was small (only 45 patients) • Used cycles of therapy as surrogate for response • Limitations of health outcomes analysis • Lack of laboratory values • Limited to one-year follow-up • Residual bias post-matching AMIA 2017 | amia.org

  18. Next Step – Validation of Results • Peripheral blood biomarker feasibility • Current prospective clinical trial to assess cytokine or immune cell profiles in Non-Small Cell Lung Cancer Patients treated with ICI compared to patients with chronic inflammation • Follow-up of clinical study participants is ongoing to analyze influence of chronic inflammation on overall survival Clinical Study Protocol AMIA 2017 | amia.org

  19. Thank you! Email me at: smelrefai@uky.edu

  20. AMIA is the professional home for more than 5,400 informatics professionals, representing frontline clinicians, researchers, public health experts and educators who bring meaning to data, manage information and generate new knowledge across the research and healthcare enterprise. AMIA 2017 | amia.org

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