Neutrophil:lymphocyte ratios and serum cytokine changes after hepatic artery chimeric antigen receptor-modified T-cell infusions for liver metastases

Our phase I Hepatic Immunotherapy for Metastases (HITM) trial tested the safety of chimeric antigen receptor-modified T-cell (CART) hepatic artery infusions (HAI) for unresectable carcinoembryonic antigen (CEA)+ liver metastases (LM). High neutrophil: lymphocyte ratios (NLR) predict poor outcome in cancer patients and we hypothesized that NLR changes would correlate with early responses to CAR-T HAI. Six patients completed the protocol. Three patients received CAR-T HAI in dose escalation (1 x 10(8), 1 x 10(9) and 1 x10(10) cells) and the remainder received three doses (1 x10(10) cells) with interleukin (IL)2 support. Serum cytokines and NLR were measured at multiple time points. The mean NLR for all patients was 13.9 (range 4.8-38.1). NLR increased in four patients following treatment with a mean fold change of 1.9. Serum IL6 levels and NLR fold changes demonstrated a trend towards a positive correlation (r=0.77, P=0.10). Patients with poor CEA responses were significantly more likely to have higher NLR level increases (P=0.048). Increased NLR levels were associated with poor responses following CAR-T HAI. NLR variations and associated cytokine changes may be useful surrogates of response to CAR-T HAI.