Abstract 666P
Background
Immunotherapy has become an important treatment modality for recurrent or metastatic nasopharyngeal carcinoma(R/M NPC). The treatment response however appears to be lower than expected, and there are remarkable individual differences that cannot be predicted. The primary aim of this study was to explore predictive biomarkers for treatment response to immunotherapy in R/M NPC.
Methods
Study population included patients with R/M NPC patients enrolled in the prospective trial (NCT 04396886) and treated with bintrafusp alfa. The counts of circulating white blood cell (WBC), neutrophil (Neu), lymphocyte (Lym), monocyte (Mon), platelet (plt), and lymphocyte subtypes consisting of CD3+T/CD19+B ratio(T/B), CD4+T, CD8+ T, CX3CR1+CD8+ T, NKT, NK, CD45RA+ CD4+ T, CD45RA+ CD8+ T, Treg, Th1, Th2, Th17, and Tfh cells were tested at baseline, cycle4 and cycle8. Treatment responses were assessed at 2 months using RECIST1.1.
Results
A total of 38 patients enrolled. There were remarkable variations of all types of immune cells at all time points. On cycle4, the levels of WBC, Mon, and NKT increased (ps<0.05). Lym increased constantly up to cycle8. However, the levels of TGF- β1, T/B, CX3CR1+CD8+T, and Th17 decreased from baseline to cycle8 (ps<0.01). Interestingly, there were significant differences between responders (2 complete responses and 7 partial responses) and non-responders (4 stable disease and 25 progressive disease). At cycle4, WBC, Neu, and Mon increased significantly in non-responders (ps<0.05), but not in responders. Of lymphocyte subtypes, the baseline Th17/Treg was remarkably lower in non-responders than that of the responders (p<0.01). T/B decreased (p<0.05) until cycle8, while the levels of CX3CR1+ CD8 T, Th17, and Th17/Treg decreased significantly in responders (ps<0.05) from cycle4 to cycle8. Plasma CX3CL1(CX3CR1 ligand) had a strong correlation with EBV DNA (0.947, p<0.000), and both were related to treatment response (ps<0.05), independent of the TGF- β1 level.
Conclusions
This study demonstrated significant differences in circulating lymphocytes and changes between responders and non-responders, suggesting a potential of biomarkers for R/M NPC to immunotherapy response. Validation studies are warranted.
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.