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).
(1) Department of Immunobiology, Yale University School of Medicine, New Haven, USA.
(2) Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain.
(3) CIBERONC (Centro de Investigación Biomedica en Red de Cáncer).
(4) Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
(5) Comprehensive Cancer Center Section of Medical Oncology, Yale University School of Medicine, New Haven, CT, USA.
(6) Department of Biochemistry, Clínica Universidad de Navarra, Pamplona, Spain.
(7) Centro de Investigación Biomédica en Red de Oncología (CIBERONC), Spain.
(8) Department of Dermatology, Yale University School of Medicine, New Haven, USA.
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.