Monitoring of NK cell activity and serum LDH in metastatic melanoma patients treated with DTIC and interferon-alpha2a, with or without retinoic acid

Abstract

19000 Background: The activity of NK cells, expression of CD69, and serum LDH were evaluated in terms of response to therapy in metastatic melanoma patients. Methods: In phase II clinical study metastatic melanoma (MM) patients were treated with DTIC (800 mg/m2, d1) and IFN-alpha 2a (5×106 IU/m2 s.c., d2–6 (group A, n=25) and 28 patients received the same therapy supplemented with RA, 60 mg/d, d1–10 (group B). Before and after each therapy cycle NK cell activity, CD69+NKcells and LDH were monitored in patients and 39 healthy controls. Results: There is no significant difference in OR (group A 32%, B 21%), in time to progression between groups. NK cell activity was significantly decreased pretherapy in both groups, with a significant increase in the 1st cycle in both groups. NK cell activity did not show significant correlation with OS in group A compared to group B (p=0.445). 20% of patients in group A with pretherapy NK cell cytotoxicity above 30% had better survival from month 3 to 12 of follow-up and a longer maximal survival (1.2 vs. 1.0 year, respectively). In comparison to pre-therapy values, all responding MM patients had a significantly higher increase of CD69 expression on CD56+ NK cells, while the increase was only significantly higher in responders in group B. Analyses of serum LDH level show a significantly higher time and therapy cycle-dependent decrease in group A compared to group B (50% vs. 25%, respectively). However, it is shown that responders in group B had a significantly greater decrease in serum LDH level compared to responders in group B (70% vs. 20%, respectively), if the level after a cycle was evaluated in terms of pretherapy values, as well as a greater decrease if the evaluation in each cycle was done compared to each pretherapy value (35% vs. 20%, respectively). Conclusions: Even though there is no significance in clinical response between patients in group A and B, in agreement with a steady-state pattern of NK cell activity, the fact that only responders in group B had a significant increase in CD69 expression on CD56+ NK cells, as well as the finding that the decrease in serum LDH was significantly greater in patients in group B, implicates favorable imunopotentiating and antitumor effect of RA in the therapy of metastatic melanoma. No significant financial relationships to disclose.