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Factors Associated With Response to High-Dose Interleukin-2 in Patients With Metastatic Melanoma

From the Surgery Branch and Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Address reprint requests to Steven A. Rosenberg, MD, PhD, Surgery Branch, National Cancer Institute, National Institutes of Health, Bldg 10, Rm 2B42, 9000 Rockville Pike, Bethesda, MD 20892-1502; email: steven_rosenberg{at}nih.gov

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 (P₂ = .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; P₂ = .0095); however, when limited to patients who were able to complete both cycles of course 1, there was no statistically significant difference (P₂ = .27). Responders had a higher maximum lymphocyte count immediately after therapy compared with nonresponders (P₂ = .0026). The development of abnormal thyroid function tests and vitiligo after therapy was associated with response (thyroid-stimulating hormone, P₂ = .01; free T4, P₂ = .0049; vitiligo, P₂ < 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.

Presented at the Thirty-Seventh Annual Meeting of the American Society of Clinical Oncology, May 12-15, 2001, San Francisco, CA.

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