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

Abstract

Purpose: 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.Experimental Design: 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.Results: 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 Â 10 7 ), but 15 samples of plasma with a median of 867 copies/mL (range: 0-1.27 Â 10 7 ). Results of these 2 measurements of EBV-DNA well correlated (R 2 ¼ 0.994, P < 0.001). The overall response rate to SMILE was significantly higher in patients with less than 10 5 copies/mL of EBV-DNA in whole blood at enrollment (90% vs. 20%, P ¼ 0.007) and in patients with less than 10 4 copies/mL of EBV-DNA in plasma (95% vs. 29%, P ¼ 0.002). The incidence of grade 4 toxicity of SMILE other than leukopenia/neutropenia was significantly higher in patients with 10 5 copies/mL of EBV-DNA or more in whole blood (100% vs. 29%, P ¼ 0.007) than that of others and in patients with 10 4 copies/mL or more in plasma (86% vs. 26%, P ¼ 0.002). Conclusions: 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. Clin Cancer Res; 18(15); 4183-90. Ó2012 AACR.

Retrospective Study of Pegaspargase, Gemicitabine, Oxaliplatin and Dexamethasone (Peg-GemOD) as a First-Line Therapy for Advanced-Stage Extranodal NK/T Cell Lymphoma

“…Several studies have shown that plasma EBV-DNA level is a sensitive surrogate biomarker for ENKTL tumor load. Persistently undetectable plasma EBV-DNA in ENKTL patients following treatment is correlated with superior survival [19,20]. In this study, patients who achieved undetectable plasma EBV-DNA following treatment with the Peg-GemOD regimen were still alive and maintained CR status, which indicates that plasma EBV-DNA level is an independent predictor for OS and PFS in advanced-stage ENKTL.…”

Clinical implications of plasma Epstein-Barr virus DNA in early-stage extranodal nasal-type NK/T-cell lymphoma patients receiving primary radiotherapy

“…In contrast, Suzuki et al reported that pretreatment plasma EBV-DNA was detectable in only 43.8% (14 of 32) of patients, 35 which was lower than both ours and other previous studies. [31][32][33] Interestingly, in a recent study, 42 EBV-DNA was detected in whole blood in 22 of 26 (84.6%) patients who received SMILE (steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy. The different percentages of detectable pretreatment EBV-DNA in previous studies are probably the result of small sample sizes, sample collection differences, and different experimental assay, in addition to other unknown factors.…”

NCCN Guidelines Insights: T-Cell Lymphomas, Version 2.2018

“…[13][14][15][16] In the phase II study from the NK-Cell Tumor Study Group, the overall response rate (ORR) was significantly higher in patients with …”