CD40 agonists have been under development for more than 20 years but have yet to become FDA approved. Pre-clinical models of cancer have shown the therapeutic potential for CD40 agonists in cancer. In addition, clear biomarkers of biological activity with CD40 activation have been defined, such as the release of cytokines (IFNg, CCL2) and the activation of monocytes, B cells and dendritic cells. However, these PD markers do not associate with outcomes. We recently found that the neutrophil to lymphocyte ratio (NLR) was a strong and simple prognostic marker of outcome in patients receiving CD40 agonist therapy with chemotherapy (1). Here, a high NLR associates with poor outcome whereas a low NLR associates with a more favorable outcome. Notably, this is a simple and translatable biomarker for selecting patients receiving CD40 immunotherapy. High NLR is an indicator of systemic inflammation and poor ‘immune health’. While many other downstream biomarkers determined by IHC, flow cytometry, or sequencing may also associate with outcomes, the NLR is perhaps the simplest and most straightforward approach to patient selection. It is suggest that trials incorporating immunotherapy should routinely report and discuss this biomarker (i.e. NLR) which may also help provide an assessment of the immunological status of the patients enrolled.
References:
Wattenberg et al. Systemic inflammation is a determinant of outcomes of CD40 agonist-based therapy in pancreatic cancer patients. JCI Insight. 2021 Mar 8;6(5):e145389
