Follow up of soluble IL‐2 receptor level in metastatic malignant melanoma patients treated by chemoimmunotherapy

Immunological parameters following chemoimmunotherapy combination were studied in 31 patients with metastatic malignant melanoma. They received Cisplatin (100 mg/m2) on day 1 and 28, recombinant IL-2 (rIL-2; Eurocetus) in continuous infusion from day 3 to 6, 17 to 21, 31 to 34 and 45 to 49. Interferon-alpha (IFN-alpha; Roche) was given subcutaneously three times weekly. No significant change in CD4/CD8 ratio at onset or during treatment was observed between responder (n = 19) and non-responder (n = 12) patients. Regarding the IL-2 receptor (IL-2R) study, the percentage of cells expressing Tac (p55) receptor did not change either for healthy volunteers (n = 20) and patients before any therapy, or between responder and non-responder patients. Concerning serum soluble IL-2R shedding before therapy, we observed a significant increase (P = 0.001) in patients (79 +/- 40 pM) compared with healthy donors (30 +/- 15 pM), but no significant variation was seen between responder and non-responder patients. In contrast, during the treatment, the soluble IL-2R level increased in both groups but, interestingly, a significant difference was found between responder and non-responder patients from day 7 (P < 0.05) to day 21 (P < or = 0.01), suggesting that the cells from non-responder may be slower in becoming stimulated. This finding is the most striking point of our study and suggests that sIL-2R might be an early predictive factor of the clinical response as obtained by logistic regression (P = 0.0063). Therefore patients with a serum soluble IL-2R level greater than 250 pM at day 21 have a 12-fold more chance of undergoing a clinical response.