Abstract A51: Quantitative assessment of VEGF combined with known clinical variables predicts outcome in patients with diffuse large B-cell lymphoma (DLBCL): Implications for guiding future treatment selection.

Introduction: The pathogenesis of DLBCL is both complex and heterogeneous, and pathogenetic mechanisms remain largely unknown. A clinical index known as the international prognostic index (IPI) remains the ‘gold-standard’ for predicting response to therapy and overall survival; however, more recently, several groups have reported the utility of gene expression arrays to sub-classify patients and predict outcome. We sought to interrogate a series of biomarkers with multiplex quantitative immunofluorescence (QIF) to construct novel clinical algorithms which predict treatment response and overall survival (OS) post-treatment in a series of patients with DLBCL. Methods: Clinical data including outcome and tissue microarray (TMA) cores for 149 patients were evaluated with QIF for association with response to standard chemotherapy and rituximab. Multiplex QIF with CRI Nuance imaging software for MUM1, Ki67, CD20, CD34, BCL2, BCL6, CD68, VEGF, HLA-DR, and NfKB. Kaplan-Meier survival function curves, hazard ratio and concordance index (CoI) were used to associate marker expression with OS and response to therapy. Results: The cohort demographics for the 149 patients include a median age of 61 years; 43% female, 57% male and an IPI breakdown: Stage1 (30%), II (23%), III (25%) and IV (22%). Both low IPI and female gender were reliable predictors of good overall survival (p 3.84, p=0.003) was found to be significant in predicting poor OS. An expanded patient cohort will be needed to confirm both results, especially the BCL6 expression profiles. Optimal multivariate model to predict OS consisted of: Age, IPI index and VEGF levels (CoI 0.78, p=0.001), compared to a model with just age and IPI (CoI 0.72, p=0.02). Conclusion: CD68, VEGF and BCL6 appear to be useful markers for understanding patterns of response and outcome for patients with DLBCL, post-treatment. A combined age, IPI and VEGF clinical algorithm may guide future treatment options for selected individuals. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr A51.