Abstract LB-165: Low TCR diversity (divpenia) is a new prognosis factor of overall survival in metastatic breast cancer

Abstract

Abstract Rationale Lymphopenia (<1000 Lymphocytes/μl) or CD4+ T cell lymphopenia (<450/μl), detected before initiation of chemotherapy are predictive factors for toxicity and death in metastatic solid tumors (Borg et al 2004; Ray Coquard et al 2009). The goal of the present study was to further identify the characteristics of the T cells in these lymphopenic patients. TCR diversity was investigated and tested as predictive factor for overall survival (OS). Patients and methods The ImmunTraCkeR® assay (ImmunID, Grenoble France), which analyzes, through semi quantitative multiplex PCR, the V-D-J combinatorial diversity of TCR-beta chain (TRB), was used to investigate diversity of T cell repertoire on cryopreserved blood samples from a prospective cohort of untreated metastatic breast cancer patients (SEMTOF study)(n=66). Univariate and multivariate analysis of prognostic factors for OS were investigated in this series as well as in a validation series. Results A severe T cell Divpenia (T cell diversity below 33%) (average diversity for healthy people is 70%) was associated with median survival of 9 months vs 24 months for the remaining patients (logrank p.value=0.0047). In a multivariate analysis, including haemoglobin level, polynuclear neutrophil count and liver metastasis, divpenia (defined at 30% threshold defined by ROC curve analysis) was identified as an independent prognostic factor. The NDL® score (Numeration Diversity Lymphocytes representation) that combines lymphocytes numeration with TRB diversity, demonstrated that lympho-divpenia (T cell diversity below 33% and lymphopenia at 1Giga/L threshold) was associated with a poor prognosis in term of patients survival compared to patients with either a good numeration or good diversity or both good numeration and diversity (p.value=0.0202). Prognostic value of NDL® score was then evaluated on a prospective validation cohort of 33 patients (logrank p.value=0.002). Conclusion: Divpenia, and a combined parameter NDL are predictive factors for survival in metastatic breast cancer patients. An open clinical study (LYMPHOS1) will investigate divpenia and NDL® score in a larger prospective cohort of metastatic breast patients. Acknowledgments M.MANUEL is a CIFRE recipient. This work (Proof of Concept “LYMPHOS1”) was financially supported by CLARA (LYON, France) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-165. doi:10.1158/1538-7445.AM2011-LB-165