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HLA Association with Response and Toxicity in Melanoma Patients Treated with Interleukin 2-based Immunotherapy

Surgery Branch, Clinical Oncology Program, Division of Cancer Treatment [F. M. M., D. W., J. B., S. A. R., D. R. P.] and Biostatistics and Data Management Section [D. V.], National Cancer Institute, and Department of Transfusion Medicine [T. B. S.], NIH, Bethesda, Maryland 20892, and Department of Surgery, University of Pittsburgh [J. T. R., M. T. L.], Pittsburgh, Pennsylvania 15261

¹ To whom requests for reprints should be addressed, at the Surgery Branch, National Cancer Institute, Building 10, Room 2B42, Bethesda, MD 20892.

Peripheral blood lymphocytes from 146 patients with metastatic melanoma undergoing interleukin 2 (IL-2)-based immunotherapy were characterized for HLA A, B, Cw, DR, DQw, and DRw specificities. Patients had been enrolled into sequential treatment protocols with either IL-2 alone (28) or in combination with tumor-infiltrating lymphocytes (TILs) (86), -interferon (26), lymphokine-activated killer cells (16), radiation therapy (7), cyclophosphamide (3), tumor necrosis factor (1), and interleukin 4 (1) for a total of 168 courses of therapy. HLA phenotype was then correlated with response rate and toxicity to IL-2. We noted: (a) a significant difference in the frequency of A11 (20.5% versus 10.2%; P < 0.05) allele between melanoma patients and the North American Caucasian population; (b) a significantly higher frequency of A11 phenotype among responders (40.5%) than in the melanoma patient population (20.5%; P < 0.01), which was even more obvious among patients responding to TIL therapy (47.4% versus 22.1%; P < 0.05); within TIL patients, responders also had an increased frequency of A19 (42.1% versus 25.6%; P < 0.05); (c) a correlation between the number of TILs received and response rate (P < 0.005); and (d) an association between DR4 haplotype and decreased tolerance to IL-2 among the patients receiving TILs (P = 0.01). These results suggest that, in melanoma patients, some HLA Class I specificities may predict for a greater likelihood of response to IL-2-based therapy, while HLA Class II phenotype correlates with tolerance to the combination of TIL and IL-2 therapy.

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Received 6/12/92. Accepted 9/23/92.

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