Abstract 1403: Correlations between overall survival and patient regulatory T-cell levels at initiation of Folfiri therapy in colorectal cancer
Authors: Jochems Caroline , Cereda Vittore , Fernando Romaine I. , Richards Jacob , Grenga Italia , Ferroni Patrizia , Guadagni Fiorella , Schlom Jeffrey , Roselli Mario 
Published: July 2016

Abstract
Twenty-three patients with metastatic colon or rectal carcinoma were enrolled in a first-line study of Folfiri therapy consisting of irinotecan (180 mg/m2 day 1), levo-leucovorin (200 mg/m2 day 1), 5-FU (400 mg/m2 bolus day 1 and 2400 mg/m2 continuous infusion over 48h), and bevacizumab (5 mg/kg day 1). This treatment schedule was repeated every 2 weeks. Peripheral blood samples were collected prior to the start of cycle I, and after 30 days, and assayed by 4-color flow cytometry and regulatory T-cell (Treg) suppression assay.
Cytofluorometric analysis of PBMCs of the entire group of patients revealed no statistical differences between the PBMCs collected at baseline and post 30 days of therapy in terms of PBMC amount, percent of CD4+ T cells, CD8+ T cells, or Tregs, or the ratios of CD4+ T cells or CD8+ T cells vs. Tregs.
Lower levels of Tregs (&lt; 2.5% of PBMC) at baseline, i.e., prior to chemotherapy, were associated with a better PFS by log-rank analysis. The median PFS for patients with &lt; 2.5% Tregs at baseline was 23.3 weeks, and for patients with &gt;2.5% Tregs at baseline PFS was 10.7 weeks (p = 0.037, n = 23).
Furthermore, a forward step-wise regression analysis model demonstrated that lower Tregs at baseline (regression coefficient = 0.467, p = 0.004) and the decrease in Tregs (as% of PBMC) at 30 days of chemotherapy (regression coefficient = 0.454, p = 0.006) were both independent predictors of better OS, independent of age, gender, ALP, LDH, mucinous vs. non-mucinous phenotype, serum CEA, serum 19.9, and number of metastatic sites.
Of the 23 patients on study, 14 demonstrated clinical responses by RECIST criteria and nine did not. Eight of the 14 (57%) responders by RECIST criteria displayed Treg levels &lt; 2.5% of PBMC at baseline, whereas only two of the seven (22%) non-responders demonstrated &lt; 2.5% Tregs at baseline. In addition, nine of the responders by RECIST criteria (64%) showed a trend in the decrease of Tregs as% of PBMC at 30 days of therapy, whereas only 22% of the non-responders had a decrease in Tregs (p = 0.049, Chi2 = 3.9 with Pearson test).
In conclusion, we found lower frequencies of Tregs at baseline in responders than non-responders, which was associated with longer PFS. In addition, lower Tregs at baseline and a decrease in Treg frequency after 1 month of Folfiri therapy were both independent predictors of longer OS.
Citation Format: Caroline Jochems, Vittore Cereda, Romaine I. Fernando, Jacob Richards, Italia Grenga, Patrizia Ferroni, Fiorella Guadagni, Jeffrey Schlom, Mario Roselli. Correlations between overall survival and patient regulatory T-cell levels at initiation of Folfiri therapy in colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1403.