Data from Pretreatment EBV-DNA Copy Number Is Predictive of Response and Toxicities to SMILE Chemotherapy for Extranodal NK/T-cell Lymphoma, Nasal Type

Abstract

<div>Abstract<p><b>Purpose:</b> Extranodal NK/T-cell lymphoma, nasal type (ENKL) is an Epstein–Barr virus (EBV)–associated lymphoma for which a new chemotherapeutic regimen called SMILE (steroid, methotrexate, ifosfamide, l-asparaginase, and etoposide) recently showed promising results.</p><p><b>Experimental Design:</b> The amount of EBV-DNA was prospectively measured in whole-blood and plasma samples by real-time quantitative PCR from 26 patients registered in the SMILE phase II study.</p><p><b>Results:</b> Before treatment, the EBV-DNA was detected in 22 samples of whole blood with a median number of 3,691 copies/mL (range: 0–1.14 × 10<sup>7</sup>), but 15 samples of plasma with a median of 867 copies/mL (range: 0–1.27 × 10<sup>7</sup>). Results of these 2 measurements of EBV-DNA well correlated (<i>R</i><sup>2</sup> = 0.994, <i>P</i> < 0.001). The overall response rate to SMILE was significantly higher in patients with less than 10<sup>5</sup> copies/mL of EBV-DNA in whole blood at enrollment (90% vs. 20%, <i>P</i> = 0.007) and in patients with less than 10<sup>4</sup> copies/mL of EBV-DNA in plasma (95% vs. 29%, <i>P</i> = 0.002). The incidence of grade 4 toxicity of SMILE other than leukopenia/neutropenia was significantly higher in patients with 10<sup>5</sup> copies/mL of EBV-DNA or more in whole blood (100% vs. 29%, <i>P</i> = 0.007) than that of others and in patients with 10<sup>4</sup> copies/mL or more in plasma (86% vs. 26%, <i>P</i> = 0.002).</p><p><b>Conclusions:</b> These findings suggest that whole blood is more sensitive for clinical use than plasma. The EBV-DNA amount in whole blood was useful for predicting tumor response, toxicity, and prognosis after SMILE chemotherapy for ENKL. <i>Clin Cancer Res; 18(15); 4183–90. ©2012 AACR</i>.</p></div>