Factors associated with response to high-dose interleukin-2 in patients with metastatic melanoma

Purpose: The present study attempted to identify characteristics that correlated with clinical response to interleukin (IL)-2 therapy in patients with metastatic melanoma. Patients and Methods: We retrospectively evaluated laboratory and clinical characteristics of 374 consecutive patients with metastatic melanoma treated with high-dose intravenous bolus IL-2 (720,000 IU/kg) from July 1, 1988, to December 31, 1999, at the Surgery Branch of the National Cancer Institute. Results: The overall objective response rate was 15.5%. Pretreatment parameters such as patient demographics, laboratory values, and prior therapy did not correlate with response; however, 53.6% of patients with only subcutaneous and/or cutaneous metastases responded, compared with 12.4% of patients with disease at other sites (P-2 = .000001). During therapy, patients who were responders tended to have received more doses during course 1 (16.2 +/- 0.3 doses v 14.5 +/- 0.2 doses; P-2 = .0095); however, when limited to patients who were able to complete both cycles of course 1, there was no statistically significant difference (P-2 = .27). Responders had a higher maximum lymphocyte count immediately after therapy compared with nonresponders (P-2 = .0026). The development of abnormal thyroid function tests and vitiligo after therapy was associated with response (thyroid-stimulating hormone, P-2 = .01; free T4, P-2 = .0049; vitiligo, P-2 < 10(-6)), although thyroid dysfunction may have been related more to the length of IL-2 therapy than to response. Conclusion: The presence of metastases only to subcutaneous and/or cutaneous sites, lymphocytosis immediately after treatment, and long-term immunologic side effects, especially vitiligo, were associated with antitumor response to IL-2 therapy.