Baseline peripheral blood biomarkers associated with clinical outcome of advanced melanoma patients treated with ipilimumab. Martens, Wistuba-Hamprecht, Geukes Foppen, et al. Clin Cancer Res. 2016 Jan 19.
[This study was done as an attempt to] identify baseline peripheral blood biomarkers associated with clinical outcome following ipilimumab treatment in advanced melanoma patients.
Frequencies of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), serum lactate dehydrogenase (LDH), routine blood counts, and clinical characteristics were assessed in 209 patients. Endpoints were overall survival (OS) and best overall response. Statistical calculations were done by Kaplan-Meier- and Cox-regression-analysis including calibration and discrimination by C-statistics.
Low baseline LDH, absolute monocyte counts (AMC), Lin-CD14+HLA-DR-/low-MDSC frequencies, and high absolute eosinophil counts (AEC), relative lymphocyte counts (RLC), and CD4+CD25+FoxP3+-Treg frequencies were significantly associated with better survival, and were considered in a combination model. 43.5% of patients presenting with the best biomarker signature had a 30% response rate and median survival of 16 months. In contrast, patients with the worst biomarkers (27.5%) had only a 3% response rate and median survival of 4 months. The occurrence of adverse events correlated with neither baseline biomarker signatures nor the clinical benefit of ipilimumab. In another model, limited to the routine parameters LDH, AMC, AEC, and RLC, the number of favorable factors (4 vs. 3 vs. 2-0) was also associated with OS in the main study and additionally in an independent validation cohort.
A baseline signature of low LDH, AMC and MDSCs as well as high AEC, Tregs and RLC is associated with favorable outcome following ipilimumab. Prospective investigation of the predictive impact of these markers following ipilimumab and other treatments, e.g. PD-1 antibodies, is warranted.
So...common themes we have been seeing lately: LOW LDH, AMC and MDSC's bode well for those treated with immunotherapy. More related info here:
LDH as predictor of outcome
Being female with low LDH and no ulceration...good with BRAFi
Neutrophils as prognostic predictor
Markers for response to immunotherapy
How to make anti-PD1 work better
Have a beautiful weekend! -c