Correlation between serum adenosine deaminase activity and efficacy of anti-programmed cell death-1 antibody

Lung Cancer. 2019 Jul:133:4-9. doi: 10.1016/j.lungcan.2019.04.022. Epub 2019 Apr 27.

Abstract

Objective: Serum adenosine deaminase (ADA) activity is a marker of immune reaction to several diseases. We evaluated changes in serum ADA in patients with lung cancer undergoing chemotherapy or anti-programmed cell death-1 (PD-1) therapy to examine the correlation between serum ADA and the therapy efficacy.

Materials and methods: We assessed 50 patients with advanced lung cancer receiving chemotherapy or anti-PD-1 therapy. Serum ADA was measured before and on day 7 of the first treatment cycle and day 0 of subsequent cycles. Correlations between ADA change and efficacy of treatment were evaluated.

Results: Of the 50 patients, 20 were treated with chemotherapy and 30 were treated with anti-PD-1 therapy. Serum ADA decreased significantly between baseline and day 7 of the first cycle in patients undergoing chemotherapy, regardless of response (partial response [PR] or stable disease [SD]: -23% [-38 to +32; p = 0.002]; progressive disease [PD]: -12% [-42 to +6; p = 0.500]). Conversely, in patients undergoing anti-PD-1 therapy, serum ADA increased significantly between baseline and 7 days after the first dose and before subsequent doses in patients who had PR or SD. (day 7 of first cycle: +6% [-10 to +34; p = 0.034], day 0 of second cycle: 8% [-5 to +37; p = 0.002], day 0 of third cycle: 9% [-3 to +55; p = 0.002]). However, serum ADA did not significant change in PD patients undergoing anti-PD-1 therapy. Furthermore, early increases in serum ADA were associated with longer progression-free survival in patients receiving anti-PD-1 therapy (p = 0.006).

Conclusion: Changes in serum ADA could be used to predict clinical benefit from anti-PD-1 therapy in patients with lung cancer. The association between changes in serum ADA and the efficacy of ant-PD-1 therapy thus remains inconclusive and requires further study.

Keywords: Adenosine deaminase; Anti-programmed cell death-1 therapy; Immune checkpoint inhibitor; Lung cancer.

MeSH terms

  • Adenocarcinoma of Lung / metabolism
  • Adenocarcinoma of Lung / mortality
  • Adenocarcinoma of Lung / therapy*
  • Adenosine Deaminase / blood*
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / blood*
  • Female
  • Humans
  • Immunotherapy / methods*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality
  • Lung Neoplasms / therapy*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Nivolumab / therapeutic use*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Survival Analysis

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab
  • pembrolizumab
  • Adenosine Deaminase