Predictive value of immunotherapy-induced inflammation indexes: dynamic changes in patients with nasopharyngeal carcinoma receiving immune checkpoint inhibitors

Abstract

Background: Immune checkpoint inhibitors (ICIs) have achieved substantial advancements in clinical care. However, there is no strong evidence for identified biomarkers of ICIs in NPC.

Methods: In this retrospective study, 284 patients were enrolled into a training or validation cohort. Inflammatory indexes based on peripheral blood parameters were evaluated, including the systemic immune-inflammation index (SII), the neutrophil-lymphocyte ratio (NLR), the platelet-lymphocyte ratio (PLR), the lymphocyte-to-C-reactive protein ratio (LCR), and the lymphocyte-monocyte ratio (LMR). The optimum cut-off value for patient stratification was identified using X-tile. The Kaplan-Meier method and Cox's proportional regression analyses were used to identify prognostic factors.

Results: Immunotherapy significantly changed the levels of SII, NLR, PLR, LCR and LMR in NPC patients. Patients with lower SII, NLR, and PLR, as well as those with higher LCR and LMR, before immunotherapy had superior PFS (all p < 0.05). Moreover, PFS in the decreased SII, reduced NLR and increased LMR group was significantly longer than in the opposite group (all p < 0.05). Both univariate and multivariate analyses validated that baseline SII and LMR, and the immunotherapy-related SII reduction and LMR elevation were independent prognostic factors for PFS in advanced NPC patients receiving ICIs.

Conclusions: Immune checkpoint inhibitor treatments significantly changed the levels of SII, NLR, PLR, LCR and LMR in NPC patients treated with immunotherapy. A lower baseline SII and a higher baseline LMR, and a reduction in SII and an elevation in LMR after immunotherapy are favorable factors for predicting survival among advanced NPC patients.

Keywords: NPC; immune checkpoint inhibitors; inflammatory and immune-based prognostic indexes; prognosis.

Figure 1.

Survival curves according to the cutoff levels of baseline SII, NLR, PLR, LCR, and LMR determined by X-tile. (A) Significant difference in PFS between patients with baseline SII higher than 947.82 and those with SII lower than 947.82 (6.27 months vs 11.43 months, P < 0.001) in the training cohort. (B) Significant difference in PFS between patients with baseline NLR lower than 3.17 and those with NLR higher than 3.17 (11.43 months vs 6.3 months, P = 0.0014) in the training cohort. (C) Significant difference in PFS between patients with baseline PLR lower than 253.52 and those with PLR higher than 253.52 (9.5 months vs 6.1 months, P = 0.0335) in the training cohort. (D) Significant difference in PFS between patients with baseline LCR higher than 0.03 and those with LCR lower than 0.03 (9.6 months vs 3.95 months, P = 0.0009) in the training cohort. (E) Significant difference in PFS between patients with baseline LMR higher than 1.34 and those with LMR lower than 1.34 (9.4 months vs 1.78 months, P < 0.001) in the training cohort. (F) Significant difference in PFS between patients with baseline SII higher than 947.82 and those with SII lower than 947.82 (8.17 months vs 17.9 months, P = 0.0423) in the validation cohort. (G) Significant difference in PFS between patients with baseline NLR lower than 3.17 and those with NLR higher than 3.17 (17.9 months vs 12.6 months, P = 0.016) in the validation cohort. (H) Significant difference in PFS between patients with baseline PLR lower than 253.52 and those with PLR higher than 253.52 (16.97 months vs 10.67 months, P = 0.0476) in the validation cohort. (I) Significant difference in PFS between patients with baseline LCR higher than 0.03 and those with LCR lower than 0.03 (17 months vs 8.17 months, P = 0.0456) in the validation cohort. (J) Significant difference in PFS between patients with baseline LMR higher than 1.34 and those with LMR lower than 1.34 (17.73 months vs 8.17 months, P = 0.0178) in the validation cohort.

Figure 2.

Survival curves according to fluctuations in SII, NLR, and LMR levels. (A) Significant difference in SII between patients with SII elevation and those with SII reduction after receiving immunotherapy compared to the baseline (7.13 months vs 11.27 months, P = 0.0416) in the training cohort. (B) Significant difference in NLR between patients with NLR elevation and those with NLR reduction after receiving immunotherapy compared to the baseline (6.93 months vs 11.07 months, P = 0.0412) in the training cohort. (C) Significant difference in LMR between patients with LMR elevation and those with LMR reduction after receiving immunotherapy compared to the baseline (13.3 months vs 7.1 months, P = 0.0128) in the training cohort. (D) Significant difference in SII between patients with SII elevation and those with SII reduction after receiving immunotherapy compared to the baseline (12.63 months vs 23.5 months, P = 0.0435) in the validation cohort. (E) Significant difference in NLR between patients with NLR elevation and those with NLR reduction after receiving immunotherapy compared to the baseline (12.6 months vs 17 months, P = 0.0399) in the validation cohort. (F) Significant difference in LMR between patients with LMR elevation and those with LMR reduction after receiving immunotherapy compared to the baseline (17.73 months vs 8.77 months, P = 0.005) in the validation cohort.