227MO - Characterization of minimal residual disease (MRD) post-radiotherapy (RT) in nasopharyngeal carcinoma (NPC) patients identifies a favorable subgroup with low risk of relapse

Background

Detectable plasma Epstein-Barr virus (EBV) DNA post-RT implies a poor prognosis, but Hui et al. reported a model that could sub-stratify these patients by an EBV DNA cut-off of 500 copies/mL. Detection limits however vary between different EBV DNA assays, which could lead to false positives at low EBV DNA levels. We investigated the EBV DNA kinetics and survival in patients harboring a detectable, but non-quantifiable EBV DNA post-RT (≤265 copies/mL; termed as MRD).

Methods

We curated a prospective NPC registry from a single institution for patients with at least one EBV DNA test 6 w post-RT, and a minimum follow-up of 3 y. All patients received RT+/-concurrent chemotherapy (CCRT)+/-induction (IC) or adjuvant chemotherapy (AC). Plasma EBV DNA was quantified using the BamH1 PCR-based assay that was validated against the International Standard. Disease-free survival (DFS) was used for survival analyses.

Results

224 patients were analyzed. Median follow-up was 49 mo. 71/224 (32%) patients were AJCC/UICC 8^th ed TNM-stage 1-2, and 151/224 (67%) were TNM-stage 3-4A; 138/224 (62%) and 86/224 (38%) reported a pre-RT EBV DNA of <4000 and ≥4000 copies/mL, respectively. 62/224 (28%) received RT and 162/224 (72%) received CCRT+/-IC or AC. 181/224 (81%) patients achieved a complete EBV DNA response (CR) within 6 w post-RT, while 36/224 (16%) had MRD, and 7/224 (3%) had >265 copies/mL. Patients with MRD and >265 copies/mL had significantly inferior DFS than the CR subgroup (HR 2.0[95%CI:1.2-3.5], P=0.01; HR 5.0[2.0-12.6], P<0.001). Next, we characterized the EBV DNA kinetics for 65 patients who had a repeat EBV DNA test at 14 w post-RT (39, 21, and 5 patients had an initial CR, MRD, and >265 copies/mL, respectively). 14/21 (67%) MRD patients had a subsequent CR, while 6/21 (29%) reported persistent MRD. 3-y relapse rates were highest for patients with MRD-MRD compared with MRD-CR and CR-CR (83% vs 29% and 24%).

Conclusions

We showed that among NPC patients with MRD post-RT, only those manifesting persistent MRD have a high risk of relapse. This has implications on current trials investigating the role of AC in patients with a detectable EBV DNA post-RT.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.