Markers of angiogenesis and hypoxia to cell of origin (COO) subtypes of DLBCL: Correlative studies from S0515, a phase II trial of R-CHOP plus bevacizumab

Autor: Mohammad Abu Zaid, Richard I. Fisher, Joseph M. Unger, Alison Stopeck, Marilyn T. Marron, Ambuga R. Badari, Thomas P. Miller, Lisa M. Rimsza
Rok vydání: 2013
Předmět:
Zdroj: Journal of Clinical Oncology. 31:8562-8562
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2013.31.15_suppl.8562
Popis: 8562 Background: S0515 was a nonrandomized phase 2 trial of R-CHOP + bevacizumab in 64 patients with newly diagnosed DLBCL. No significant improvement in PFS or OS was observed compared with historic controls.Patients with higher baseline levels of plasma VCAM and urine VEGF had worse PFS and OS. Tumor-associated carbonic anhydrase, CA IX, is induced by hypoxia in various tumors and part of the hypoxia inducible factor -1/ hypoxia responsive element (HIF-1/HRE) system. We present additional correlative studies from S0515 including longitudinal plasma CAIX levels, and correlate expression of VEGF and VEGF receptors (VEGFR) to COO subtype [GCB vs. non-GCB] and urine VEGF and plasma VCAM. Methods: COO subtypes were determined by immunohistochemistry (IHC) using the Hans classification. VEGF and VEGFR expression was determined by IHC and scored on a scale of 0 (none) to +3 (strong). Plasma VCAM, CAIX, urine VEGF levels were measured by ELISA and samples collected at baseline and before cycles 4 and 8 of therapy. Results: Baseline CAIX levels did not predict PFS (p = 0.95) or OS (p=.66) or change with therapy. Patients with lower baseline CAIX levels (below the median) had a statistically significant increase in CAIX over the course of therapy (median 34.1 to 52.4, p=.002), whereas in patients with higher baseline CAIX, levels decreased (median 96.7 to 78.2, p=.20). CAIX correlated with plasma VCAM (P=.006), but not COO subtype. 33 lymphoma samples were classified as GCB (n = 21) or non-GCB (n=12). COO subtype did not predict difference in PFS (p=.56) or OS (p=.67). Median urine VEGF and plasma VEGF levels trended higher in non-GCB vs GCB tumors (181 vs 144pg/mL and 1499 and 821ng/mL, respectively). Lymphoma expression of VEGF did not correlate with plasma VCAM or urine VEGF. VEGR2 expression was higher in non-GCB vs GCB tumors (33% vs 5% expression). Conclusions: Plasma CAIX levels, a marker of hypoxia and HIF1alpha activation, increased only in those patients with lower baseline levels in response to therapy. COO by IHC did not predict PFS or OS. However, non-GCB tumors had higher expression of VEGFR2, plasma VCAM, and urine VEGF compared to GCB tumors consistent with increased angiogenesis. Clinical trial information: SWOG S-0515.
Databáze: OpenAIRE
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