INCIDENCE RATE AND RISK-FACTORS FOR THYROID-DYSFUNCTION DURING RECOMBINANT INTERLEUKIN-2 THERAPY IN ADVANCED MALIGNANCIES

Immunotherapy using recombinant interleukin 2 (rIL-2) has been shown t o induce thyroid dysfunction in some cancer patients. The purpose of t he present study was to evaluate the incidence and risk factors of thi s adverse autoimmune response. Triiodothyronine, thyroxine and thyrotr opin levels were measured serially in 146 consecutive patients treated with rIL-2 for refractory solid tumor (77 patients) or malign hemopat hy (69 patients): rIL-2 was administered intravenously in 5-day cycles (18 x 10(6)-24 x 10(6) IU. m-2 . day-1) either alone in 79 cases or i n combination with autologous bone marrow transplantation in 2 6 cases , with interferon-gamma in 37 cases, with tumor necrosis factor-alpha in 13 and with cyclophosphamide in five cases. Some patients underwent more than one therapeutic protocol. Peripheral hypothyroidism was pre sent upon entry in nine (6.2%) patients. Thyroid dysfunction appeared or worsened during rIL-2 therapy in 24 (16.4%) patients. Sixteen (10.9 %) patients exhibited peripheral hypothyroidism, out of which four exh ibited biphasic thyroiditis. Another five (3.4%) patients developed tr ansient hyperthyroidism. Anomaly could not be classified in three pati ents. Thyroid dysfunction appeared early after one or two cycles. All surviving patients recovered. Only gender and presence of antithyroid antibody were correlated significantly with rIL-2-induced thyroid abno rmalities. No correlation was found with any of the other risk factors studied, i.e. type of malignancy, rIL-2 treatment procedure, clinical efficacy, evolution of circulating lymphocyte subsets or other autoim mune antibodies. Antithyroid antibodies were detected in 60.9% of pati ents with this complication. Thyroid-stimulating antibodies were never detected. In susceptible individuals, rIL-2 can activate autoreactive clones, leading to acute autoimmune thyroiditis similar to postpartum thyroiditis. The high incidence of the complications during this immu notherapy justifies systematic screening.