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

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2019-07, Vol.133, p.4-9
• Main Authors: Saiki, Masafumi, Yoshizawa, Takahiro, Dotsu, Yosuke, Ariyasu, Ryo, Koyama, Junji, Sonoda, Tomoaki, Uchibori, Ken, Nishikawa, Shingo, Kitazono, Satoru, Yanagitani, Noriko, Horiike, Atsushi, Nishio, Makoto
• Format: Article
• Language: English
• Subjects: Adenocarcinoma of Lung - metabolism; Adenocarcinoma of Lung - mortality; Adenocarcinoma of Lung - therapy; Adenosine deaminase; Adenosine Deaminase - blood; Aged; Aged, 80 and over; Anti-programmed cell death-1 therapy; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents - therapeutic use; Biomarkers, Tumor - blood; Female; Humans; Immune checkpoint inhibitor; Immunotherapy - methods; Lung cancer; 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
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2019.04.022

•Serum ADA increased from baseline in the patients who response for anti-PD-1 therapy.•Serum ADA decreased from baseline regardless of response in the chemotherapy group.•Increases in serum ADA were associated with longer PFS in anti-PD-1 group. 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. 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. 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). 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.