Changes in serum IL8 levels reflect and predict response to anti-PD-1 treatment in melanoma and non-small cell lung cancer patients

Background

Anti-PD-1 blockade effectively treats several tumor types. Yet, surrogate biomarkers of clinical benefit are needed to evaluate efficacy, given the delay in observing responses and the existence of pseudo-progressions. This work aims to evaluate serum IL8 levels as a biomarker during anti-PD-1 mAb treatment of melanoma and non-small cell lung cancer (NSCLC) patients.

Methods

44 metastatic melanoma and 19 metastatic NSCLC patients treated with anti-PD-1 mAb therapy as a single-agent, or in combination with anti-CTLA-4 mAb, were studied. Blood was withdrawn at baseline, 2-4 weeks after starting treatment, at best response and at disease progression. Serum IL8 levels were determined by sandwich ELISA. Wilcoxon test was used to compare changes in serum IL8 levels during treatment and the Mann-Whitney U test was used to assess strength of correlation between serum IL8 levels and clinical response assessed by RECIST 1.1 criteria.

Results

The discovery set consisted of 12 melanoma patients treated with anti-PD-1 mAb. In responding patients, serum IL8 levels decreased significantly at the moment of BR compared to baseline levels, and significantly increased upon progression. In non-responders, IL8 levels significantly increased at the moment of progression compared to baseline levels (Table 1). These results were confirmed in a validation set of 17 melanoma and 19 NSCLC patients similarly treated with anti-PD-1 mAbs (Table 1). Additionally, we observed that early changes in serum IL8 levels (2-4 weeks after treatment initiation) strongly correlate with response in the melanoma discovery set (p = 0.05), melanoma validation set (p = 0.001), NSCLC set (p = 0.001) and in a group of 15 melanoma patients treated with anti-CTLA-4 in combination with anti-PD-1 mAbs (p = 0.001).