Alex K Bryant1, Kamya Sankar2, Garth W Strohbehn3, Lili Zhao4, David Elliott1, Angel Qin2, Sarah Yentz2, Nithya Ramnath5, Michael D Green6. 1. Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA; Department of Radiation Oncology, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI, USA. 2. Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. 3. Section of Hematology Oncology, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI, USA; VA Center for Clinical Management and Research, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI, USA. 4. Department of Biostatistics, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA. 5. Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Section of Hematology Oncology, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI, USA. Electronic address: nithyar@med.umich.edu. 6. Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA; Department of Radiation Oncology, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Microbiology and Immunology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Graduate Program in Immunology, University of Michigan School of Medicine, Ann Arbor, MI, USA. Electronic address: migr@med.umich.edu.
Abstract
BACKGROUND: Elevated pre-treatment neutrophil-to-lymphocyte ratio (NLR) may reflect immune dysfunction and is negatively prognostic in cancer patients treated with immunotherapy, but it is unclear if NLR is predictive of immunotherapy benefit. METHODS: We identified stage III non-small-cell lung cancer (NSCLC) patients treated with definitive chemoradiation and adjuvant durvalumab within the national Veterans Affairs system from 2017 to 2021. We compared the prognostic value of NLR measured before durvalumab start to a control group of stage III NSCLC patients treated with definitive chemoradiation alone from 2015 to 2016 (no-durvalumab group) before the approval of adjuvant durvalumab. We estimated the predictive value of NLR through the statistical interaction of durvalumab group by NLR level. Outcomes included progression-free survival (PFS) and overall survival (OS). RESULTS: The primary analysis for NLR included 821 durvalumab patients and 445 no-durvalumab patients. Higher NLR was associated with inferior PFS in both groups (no-durvalumab: adjusted HR [aHR] 1.14 per 7.43 unit increase in NLR, 95% confidence interval [CI] 1.06-1.23; durvalumab: aHR 1.42, 95% CI 1.23-1.64), though this effect was greater in durvalumab patients (p for interaction = 0.009). Similar results were found for OS (no-durvalumab: aHR 1.16, 95% CI 1.09-1.24; durvalumab: aHR 1.48, 95% CI 1.25-1.76; p for interaction = 0.010). Absolute lymphocytes, eosinophils, and basophils were not prognostic in either group. Estimates of durvalumab treatment efficacy suggested declining efficacy with higher NLR. CONCLUSION: Pre-treatment NLR is especially prognostic among stage III NSCLC patients treated with adjuvant immunotherapy compared to control patients treated without immunotherapy and may be a predictive biomarker of immunotherapy benefit. Published by Elsevier B.V.
BACKGROUND: Elevated pre-treatment neutrophil-to-lymphocyte ratio (NLR) may reflect immune dysfunction and is negatively prognostic in cancer patients treated with immunotherapy, but it is unclear if NLR is predictive of immunotherapy benefit. METHODS: We identified stage III non-small-cell lung cancer (NSCLC) patients treated with definitive chemoradiation and adjuvant durvalumab within the national Veterans Affairs system from 2017 to 2021. We compared the prognostic value of NLR measured before durvalumab start to a control group of stage III NSCLC patients treated with definitive chemoradiation alone from 2015 to 2016 (no-durvalumab group) before the approval of adjuvant durvalumab. We estimated the predictive value of NLR through the statistical interaction of durvalumab group by NLR level. Outcomes included progression-free survival (PFS) and overall survival (OS). RESULTS: The primary analysis for NLR included 821 durvalumab patients and 445 no-durvalumab patients. Higher NLR was associated with inferior PFS in both groups (no-durvalumab: adjusted HR [aHR] 1.14 per 7.43 unit increase in NLR, 95% confidence interval [CI] 1.06-1.23; durvalumab: aHR 1.42, 95% CI 1.23-1.64), though this effect was greater in durvalumab patients (p for interaction = 0.009). Similar results were found for OS (no-durvalumab: aHR 1.16, 95% CI 1.09-1.24; durvalumab: aHR 1.48, 95% CI 1.25-1.76; p for interaction = 0.010). Absolute lymphocytes, eosinophils, and basophils were not prognostic in either group. Estimates of durvalumab treatment efficacy suggested declining efficacy with higher NLR. CONCLUSION: Pre-treatment NLR is especially prognostic among stage III NSCLC patients treated with adjuvant immunotherapy compared to control patients treated without immunotherapy and may be a predictive biomarker of immunotherapy benefit. Published by Elsevier B.V.
Entities:
Keywords:
Durvalumab; Immunotherapy; Neutrophil-to-lymphocyte ratio; Non-small-cell; stage III
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