Background: Peripheral blood parameters are correlated to immune-checkpoint inhibitor efficacy in solid tumors, such as melanoma and non-small cell lung cancer. Few data are currently available on the prognostic role of these immune-inflammatory biomarkers for other solid tumors and immunotherapy combinations. Material and Methods: From August 2014 to May 2019, 153 patients with metastatic solid tumors were enrolled in phase I clinical trials testing immunotherapy both as single agents and as combinations. Primary endpoint was to evaluate the impact of baseline blood parameters on progression-free survival (PFS) and overall survival (OS). Results: The most common tumor types were gastrointestinal, breast, and gynecological cancers (22.9%, 22.2%, and 15.0%, respectively). Higher lactate dehydrogenase (LDH) and derived neutrophil-to-lymphocyte ratio (dNLR) were independently associated with reduced PFS (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.30–2.99; p =.001, and HR, 2.29; 95% CI, 1.39–3.77; p =.001, respectively) and reduced OS (HR, 2.04; 95% CI, 1.26–3.28; p =.004, and HR, 2.06; 95% CI, 1.12–3.79; p =.02, respectively). In the subgroup analysis, (single agent vs. combination), patients at “good” (dNLR <3 and LDH < upper limit of normal [ULN]) and “intermediate and poor” (dNLR >3 and/or LDH > ULN) risk had higher and lower PFS, respectively (p for interaction =.002). Conversely, patients receiving monotherapy presented statistically significant difference in OS according to the risk group, whereas this effect was not observed for those treated with combinations (p for interaction =.004). Conclusion: Elevated LDH and dNLR are associated with poorer survival outcomes in patients treated with immunotherapy in phase I clinical trials, regardless of tumor type. These parameters represent an easy tool that might be considered as stratification factors in immunotherapy-based clinical trials. Implications for Practice: In this retrospective cohort study of 153 patients with metastatic solid tumors treated with immunotherapy in the context of phase I clinical trials, elevated baseline lactate dehydrogenase and derived neutrophil-to-lymphocyte ratio were associated with reduced survival regardless of tumor subtype. If prospectively validated, these parameters might represent low-cost and easy biomarkers that could help patient selection for early phase immunotherapy trials and be applied as a stratification factor in randomized studies testing immunotherapy agents.

Pretreatment Blood Parameters Predict Efficacy from Immunotherapy Agents in Early Phase Clinical Trials / C. Criscitiello, A. Marra, S. Morganti, P. Zagami, G. Viale, A. Esposito, G. Curigliano. - In: THE ONCOLOGIST. - ISSN 1083-7159. - 25:11(2020), pp. e1732-e1742. [10.1634/theoncologist.2020-0518]

Pretreatment Blood Parameters Predict Efficacy from Immunotherapy Agents in Early Phase Clinical Trials

C. Criscitiello
;
S. Morganti;P. Zagami;G. Curigliano
Conceptualization
2020

Abstract

Background: Peripheral blood parameters are correlated to immune-checkpoint inhibitor efficacy in solid tumors, such as melanoma and non-small cell lung cancer. Few data are currently available on the prognostic role of these immune-inflammatory biomarkers for other solid tumors and immunotherapy combinations. Material and Methods: From August 2014 to May 2019, 153 patients with metastatic solid tumors were enrolled in phase I clinical trials testing immunotherapy both as single agents and as combinations. Primary endpoint was to evaluate the impact of baseline blood parameters on progression-free survival (PFS) and overall survival (OS). Results: The most common tumor types were gastrointestinal, breast, and gynecological cancers (22.9%, 22.2%, and 15.0%, respectively). Higher lactate dehydrogenase (LDH) and derived neutrophil-to-lymphocyte ratio (dNLR) were independently associated with reduced PFS (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.30–2.99; p =.001, and HR, 2.29; 95% CI, 1.39–3.77; p =.001, respectively) and reduced OS (HR, 2.04; 95% CI, 1.26–3.28; p =.004, and HR, 2.06; 95% CI, 1.12–3.79; p =.02, respectively). In the subgroup analysis, (single agent vs. combination), patients at “good” (dNLR <3 and LDH < upper limit of normal [ULN]) and “intermediate and poor” (dNLR >3 and/or LDH > ULN) risk had higher and lower PFS, respectively (p for interaction =.002). Conversely, patients receiving monotherapy presented statistically significant difference in OS according to the risk group, whereas this effect was not observed for those treated with combinations (p for interaction =.004). Conclusion: Elevated LDH and dNLR are associated with poorer survival outcomes in patients treated with immunotherapy in phase I clinical trials, regardless of tumor type. These parameters represent an easy tool that might be considered as stratification factors in immunotherapy-based clinical trials. Implications for Practice: In this retrospective cohort study of 153 patients with metastatic solid tumors treated with immunotherapy in the context of phase I clinical trials, elevated baseline lactate dehydrogenase and derived neutrophil-to-lymphocyte ratio were associated with reduced survival regardless of tumor subtype. If prospectively validated, these parameters might represent low-cost and easy biomarkers that could help patient selection for early phase immunotherapy trials and be applied as a stratification factor in randomized studies testing immunotherapy agents.
Settore MED/06 - Oncologia Medica
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/824874
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