# A dynamic immune response index combining C-reactive protein and lactate dehydrogenase kinetics is associated with outcomes of PD-1 inhibitor monotherapy in recurrent/metastatic nasopharyngeal carcinoma

## TL;DR

A new immune response index combining C-reactive protein and lactate dehydrogenase helps predict treatment outcomes for patients with advanced nasopharyngeal cancer receiving PD-1 inhibitors.

## Contribution

A novel dynamic immune response index integrating CRP and LDH kinetics improves outcome prediction in RM-NPC patients treated with PD-1 inhibitors.

## Key findings

- The pretreatment IRI stratified patients into risk groups with significantly different response rates and survival outcomes.
- The on-treatment IRI further refined predictions, identifying patients with high ORR and prolonged survival.
- The dynamic IRI model outperformed single-marker kinetics in predicting primary refractory disease.

## Abstract

Reliable biomarkers associated with outcomes of PD-1 inhibitor monotherapy in recurrent/metastatic nasopharyngeal carcinoma (RM-NPC) are lacking. We developed an immune response index (IRI) integrating C-reactive protein (CRP) and lactate dehydrogenase (LDH) to address this need.

In 209 RM-NPC patients receiving PD-1 inhibitor monotherapy, we constructed a pretreatment IRI using baseline CRP and LDH, and an on-treatment IRI based on their early kinetic changes. Associations with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were analyzed.

The overall ORR was 23.4% (median PFS: 3.5 months; OS: 20.2 months). The composite pretreatment IRI outperformed individual markers, stratifying patients into low-, intermediate-, and high-risk groups with ORRs of 47.8%, 17.3%, and 15.9%, respectively (P<0.0001). Corresponding median PFS was 7.3, 2.8, and 2.0 months. The on-treatment IRI further refined prediction: the good-response group (ORR 54.7%) had a median PFS of 7.5 months and OS of 31.9 months, while the poor-response group (ORR 9.4%) had a median PFS of 2.0 months. This dynamic model identified primary refractory disease more accurately than single-marker kinetics.

The CRP-LDH-based IRI, both at baseline and during early treatment, is a practical tool for stratifying prognosis and dynamically monitoring response to PD-1 inhibitors in RM-NPC, which supports ongoing clinical evaluation.