Morello S, et al. - This trial incorporated the analysis of the CD73 enzyme activity in patients with metastatic melanoma stage IV and its link with the response to nivolumab. A prominent connection was unveiled between the activity of sCD73 in the blood and clinical outcomes in patients with metastatic melanoma stage IV, receiving nivolumab. sCD73 could be used as the serologic prognostic biomarker. It was also determined that potentially evaluating sCD73 enzyme activity in the peripheral blood before treatment possibly assisted in estimating the response to nivolumab. However, the yielded data were yet to be confirmed and validated.

Methods

• The CD73 enzyme activity was examined in patients with metastatic melanoma stage IV along with its link with the response to nivolumab.
• In the serum of 37 melanoma patients, the soluble CD73 (sCD73) enzyme activity was estimated prior to receiving nivolumab.
• Through the Harrel’s C index, the best cut-off for this biomarker was identified.
• The assessment of prognostic value of CD73 enzyme activity for survival and progression-free survival was carried out via the multivariate Cox proportional hazard model.

Results

• A prominent link was disclosed between high levels of sCD73 enzyme activity with poor overall survival and progression-free survival in patients with metastatic melanoma.
• The median progression-free survival was discovered to be 2.6 months [95% confidence interval (CI) 1.9-3.3] in patients with high sCD73 enzyme activity (> 27.8 pmol/min/mg protein), and 14.2 months (95% CI 4.6-23.8) in patients with lower CD73 enzyme activity, with thw follow-up for a median of 24 months range.
• The median overall survival was not attained in patients with low sCD73 activity (< 27.8 pmol/min/mg protein) than with 6.1 months (95% CI 0-14.8) in patients with higher sCD73 activity.
• The multivariate analyses exhibited that the sCD73 enzyme activity was the strongest prognostic factor for overall survival and progression-free survival.
• Before starting nivolumab treatment, a correlation was brought to light between elevated basal levels of sCD73 enzyme activity with lower response rates to therapy.