Changes in serum interleukin-8 (IL-8) levels reflect and predict response to anti-PD-1 treatment in melanoma and non-small-cell lung cancer patients
Sanmamed MF (1), Perez-Gracia JL (2,3), Schalper KA (4,5), Fusco JP (2), Gonzalez A (3,6), Rodriguez-Ruiz ME (2,7), Oñate C (2), Perez G (2), Alfaro C (2,3), Martín-Algarra S (2), Andueza MP (2), Gurpide A (2), Morgado M (4), Wang J (1), Bacchiocchi A (8), Halaban R (8), Kluger H (5), Chen L (1), Sznol M (5), Melero I (2,6,7).
Surrogate biomarkers of efficacy are needed for anti-PD1/PD-L1 therapy, given the existence of delayed responses and pseudo-progressions. We evaluated changes in serum IL-8 levels as a biomarker of response to anti-PD-1 blockade in melanoma and non-small-cell lung cancer (NSCLC) patients.
Patients and methods:
Metastatic melanoma and NSCLC patients treated with nivolumab or pembrolizumab alone or nivolumab plus ipilimumab were studied. Serum was collected at baseline; at 2-4 weeks after the first dose; and at the time-points of response evaluation. Serum IL-8 levels were determined by sandwich ELISA.
Changes in serum IL-8 levels were compared with the Wilcoxon test and their strength of association with response was assessed with the Mann-Whitney test. Accuracy of changes in IL-8 levels to predict response was estimated using receiver operation characteristics curves.
Twenty-nine melanoma patients treated with nivolumab or pembrolizumab were studied. In responding patients, serum IL-8 levels significantly decreased between baseline and best response (P <0.001), and significantly increased upon progression (P = 0.004). In non-responders, IL-8 levels significantly increased between baseline and progression (P = 0.013).
Early changes in serum IL-8 levels (2-4 weeks after treatment initiation) were strongly associated with response (P <0.001). These observations were validated in 19 NSCLC patients treated with nivolumab or pembrolizumab (P = 0.001), and in 15 melanoma patients treated with nivolumab plus ipilimumab (P <0.001).
Early decreases in serum IL-8 levels were associated with longer overall survival in melanoma (P = 0.001) and NSCLC (P = 0.015) patients. Serum IL-8 levels also correctly reflected true response in three cancer patients presenting pseudoprogression.
Changes in serum IL-8 levels could be used to monitor and predict clinical benefit from immune checkpoint blockade in melanoma and NSCLC patients.
CITATION Ann Oncol. 2017 Aug 1;28(8):1988-1995. doi: 10.1093/annonc/mdx190.