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

BackgroundAnti-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.Methods44 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 Blood was withdrawn at baseline, 2-4 weeks after starting treatment, at best response and at disease progression.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.ResultsTabled 1Responders (clinical setting)Baseline M (Q1-Q3) pg/mlBest response M (Q1-Q3) pg/mlp (baseline vs best response)Progression M (Q1-Q3) pg/mlp (best response vs progression)Melanoma (discovery set)43.7 (36-49)13.6 (5-19)<0.0576.4 (28-130)<0.05Melanoma (validation set)110 (40-521)49 (20-78)<0.05249 (57-535)<0.05NSCLC16.3 (6-32)6 (0-17)<0.0553 (8-279)NSNon-Responders (clinical setting)Baseline M (Q1-Q3) pg/mlProgression M (Q1-Q3) pg/mlp (baseline vs progression)Melanoma (discovery set)49.8 (16-156)65 (10-147)<0.05Melanoma (validation set)41 (17-94)90 (53-178)<0.01NSCLC12 (0-42)51 (22-77)<0.05M: Median. NS: non significant. Open table in a new tab ConclusionsChanges in serum IL8 levels might be used to monitor and predict response to anti-PD-1 therapy in metastatic melanoma and NSCLC patients.Legal entity responsible for the study: Clinica Universidad de Navarra and Yale UniversityFundingGobierno de Navarra Salud, EU comission IACT and PROCRP, MINECO (SAF2008-03294, SAF2011-22831)DisclosureAll authors have declared no conflicts of interest. BackgroundAnti-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. 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. Methods44 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. 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. ResultsTabled 1Responders (clinical setting)Baseline M (Q1-Q3) pg/mlBest response M (Q1-Q3) pg/mlp (baseline vs best response)Progression M (Q1-Q3) pg/mlp (best response vs progression)Melanoma (discovery set)43.7 (36-49)13.6 (5-19)<0.0576.4 (28-130)<0.05Melanoma (validation set)110 (40-521)49 (20-78)<0.05249 (57-535)<0.05NSCLC16.3 (6-32)6 (0-17)<0.0553 (8-279)NSNon-Responders (clinical setting)Baseline M (Q1-Q3) pg/mlProgression M (Q1-Q3) pg/mlp (baseline vs progression)Melanoma (discovery set)49.8 (16-156)65 (10-147)<0.05Melanoma (validation set)41 (17-94)90 (53-178)<0.01NSCLC12 (0-42)51 (22-77)<0.05M: Median. NS: non significant. Open table in a new tab M: Median. NS: non significant. ConclusionsChanges in serum IL8 levels might be used to monitor and predict response to anti-PD-1 therapy in metastatic melanoma and NSCLC patients.Legal entity responsible for the study: Clinica Universidad de Navarra and Yale University Changes in serum IL8 levels might be used to monitor and predict response to anti-PD-1 therapy in metastatic melanoma and NSCLC patients.