Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.
Myeloid immunosuppressive state as a predictor of rapidly progressive phenotype and poor survival in advanced non-small cell lung cancer (NSCLC) patients treated with PD-1/PD-L1 inhibitors.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr e20594)
Author(s): Sally CM Lau, Lisa W Le, Sze Wah Samuel Chan, Elliot Charles Smith, Malcolm Ryan, M. Catherine Brown, Katrina Hueniken, Lawson Eng, Devalben Patel, RuiQi Chen, Alona Zer, Mike Ru Sung, Penelope Ann Bradbury, Pamela S Ohashi, Frances A. Shepherd, Ming Sound Tsao, Natasha B. Leighl, Geoffrey Liu, Adrian G. Sacher; Princess Margaret Cancer Center, Toronto, ON, Canada; Princess Margaret Hospital, Toronto, ON, Canada; Princess Margaret Cancer Centre, Toronto, ON, Canada; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada; Ontario Cancer Institute, Princess Margaret Cancer Centre, Toronto, ON, Canada; University of Toronto, Toronto, ON, Canada; Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, ON, Canada; Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada
Background: Immune subpopulations within the tumor microenvironment (TME) play a central role in determining response to checkpoint inhibitors. Myeloid derived suppressor cells, a heterogeneous population of immature myeloid cells, have a predominantly immunosuppressive role by stimulating T regulatory cells. We hypothesize that elevated myeloid-to-lymphocyte measures in the peripheral blood predict for greater numbers of myeloid derived suppressor cells in the TME and worse outcomes. Methods: In advanced NSCLC patients who received immunotherapy between 2010-2018, baseline characteristics collected retrospectively included age, sex, histology, stage, smoking status, ethnicity, PD-L1 expression and tumor genotype. Pre-treatment neutrophil/lymphocyte (NLR) and monocyte/lymphocyte ratios (MLR) were log transformed and analyzed using cox and logistic regression models. Results: Among 219 eligible patients, a high NLR was associated with shorter time-to-treatment-failure (HR 1.38, 95%CI 1.09-1.75, p = 0.008) and poorer OS (HR 1.62, 95%CI 1.23-2.14, p < 0.001), independent of PD-L1 levels. Disproportionate increases in NLR and MLR were highly correlated (Spearman’s rho = 0.78). Further, higher NLR (p = 0.09) or MLR (p = 0.06) tended to associate with best overall response (BOR) to immunotherapy, with higher rates of progressive disease (PD) and lower rates of clinical response. A high NLR (p = 0.01) and MLR (p = 0.02) were associated with a rapidly progressive phenotype defined by PD as the BOR and duration of therapy ≤2 months. This remained significant after adjusting for confounders in a multivariate model (p = 0.03 for NLR and p = 0.03 for MLR). No associations were observed between high myeloid counts and other clinical prognostic factors such as liver metastases. Conclusions: A myeloid immunosuppressive state characterized by a disproportionate increase in peripheral immune myeloid populations is significantly associated with primary refractory disease, rapidly progressive phenotype, and poorer survival. Further investigation into myeloid mediated mechanisms of resistance is warranted.