Adoptive immunotherapy with tumor-infiltrating lymphocytes and subcutaneous recombinant interleukin-2 plus interferon alfa-2a for melanoma patients with nonresectable distant disease: A phase III pilot trial

Background: On the basis of our previous experience, we designed this study to determine the activity and toxicity of outpatient treatment with autolo gous tumor-infiltrating lymphocytes (TIL) together with intermediate-dose r ecombinant interleukin-2 (rIL-2) and low-dose recombinant interferon alfa-2 a (rIFN-alpha 2a), for patients with metastatic melanoma. Methods: Between April 1992 and October 1994, we processed 38 melanoma samp les derived from 36 patients with metastases. Proliferative cultures of exp anded lymphocytes (TIL) were infused only once into patients with metastati c melanoma. rIL-2 was administered subcutaneously for 1 month, starting on the day of TIL infusion, at an escalating dose of 6-18 x 10(6) IU/m(2)/day for the first week and at the maximum-tolerated dose for the subsequent 3 w eeks and then, after a 15-day interval, for 1 week/month for 3 months. rIFN -alpha 2a was administered subcutaneously at 3 x 10(6) TCT three times each week until progression. Results: Of 38 melanoma samples, 19 (50%) resulted in proliferative culture s and were infused. The median number of expanded lymphocytes was 18 x 10(9 ) (range, 1-43 x 10(9)), and the median period of culture was 52 days (rang e, 45-60). rIL-2 was administered at doses ranging between 6 and is x 10(6) IU/m(2)/day. Toxicity was mild or moderate, and no Life-threatening side e ffects were encountered. Two of 19 treated patients experienced complete re sponses of their metastatic sites (soft tissue), 10 had stable disease, and 7 showed progressive disease. The response rate was 11% (95% confidence in terval, 2-35%). Conclusions: Outpatient treatment with TIL plus rIL-2 and rIFN-alpha 2a is feasible, although, within the context of the small sample size, the activi ty of the combination was no different from the reported activity of any of the components used alone.