Abstract 2616: Baseline blood lymphocytes are associated with improved clinical outcome in atezolizumab-treated patients across multiple indications
Authors: Li Yijin , Chang Ching-Wei , Fasso Marcella , O'Hear Carol , Hegde Priti S. , Molinero Luciana 
Published: August 2018

Background: The PD-L1/PD-1 inhibitors activate the immune system both in the tumor microenvironment and peripheral blood. Here we investigated the relationship between peripheral immune system and clinical outcome of metastatic cancer patients treated with atezolizumab (anti-PDL1) across five tumor types.

Methods: 426 patients with melanoma (n=45), non-small cell lung cancer (NSCLC, n=89), kidney cancer (RCC, n=72), triple-negative breast cancer (TNBC, n=116) and bladder cancer (UBC, n=104) were treated with atezolizumab in the phase I clinical trial PCD4989g (NCT01375842). Normal/abnormal blood neutrophils, monocytes, eosinophils, basophils and lymphocytes were measured by local laboratories, while T (CD3, CD4 and CD8), B (CD19), and NK (CD56) lymphocyte subsets were centrally analyzed by flow cytometry. Neutrophil:lymphocyte ratio (NLR) and relative lymphocyte counts (RLC) were also evaluated. Association of the immune cell subsets and clinical outcome (ORR, PFS and OS) was assessed in multivariate analyses considering liver metastases, LDH, line of therapy and ECOG performance status.

Results: The prevalence of hematologic abnormalities across tumors was: lymphopenia (27-57%), followed by neutrophilia (2-24%), monocytosis (0-15%), eosinophilia (1-13%), eosinopenia (0-14%), basophilia (2-7%) and basopenia (0-6%). Neutrophilia, monocytosis, lymphopenia and low/high eosinophils were associated with worse PFS and OS, although with a different imprint depending on tumor ontogeny: neutrophilia was linked to reduced OS in melanoma and PFS for UBC, monocytosis was associated with lower OS in TNBC and UBC. Lymphopenia was associated with reduced PFS and OS in NSCLC, TNBC and reduced PFS in melanoma. NLR&gt;=5 was associated with reduced PFS in melanoma, NSCLC, RCC, UBC and reduced OS in UBC, NSCLC and TNBC. RLC&gt;=17.5% was linked to longer PFS in melanoma, RCC, UBC and to increased OS in TNBC, NSCLC and UBC. Lymphocyte subset analysis showed lymphopenia in B cells (40-61%), CD3 T cells (32-71%), CD4 T cells (28-66%), CD8 T cells (25-46%) and NK cells (16-23%). CD3 lymphopenia was associated to reduced OS in NSCLC, and CD4 lymphopenia was associated to reduced OS in NSCLC and TNBC. NK lymphopenia was associated to decreased OS and PFS in TNBC.

Conclusion: This is the first study showing that higher pretreatment relative lymphocyte counts is associated to improved clinical outcome in patients from different tumor etiologies treated with atezolizumab. The association of peripheral T cell counts to improved outcome in some indications suggests that the local antitumor response may be linked to pre-existing systemic T cells.

Citation Format: Yijin Li, Ching-Wei Chang, Marcella Fasso, Carol O'Hear, Priti S. Hegde, Luciana Molinero. Baseline blood lymphocytes are associated with improved clinical outcome in atezolizumab-treated patients across multiple indications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2616.