Continuous interleukin‐2 and tumor‐infiltrating lymphocytes as treatment of advanced melanoma. A national biotherapy study group trial

Melanoma metastases were harvested from 82 patients for the purpose of growing and expanding tumor‐infiltrating lymphocytes (TIL). Tumor tissue cell suspensions were incubated with interleukin‐2 (IL‐2), followed by repeated exposure to tumor antigen with or without OKT3 monoclonal antibody (MoAb). Initial growth success was achieved in 56 of 82 cultures (72%). Efforts were made to expand 26 of these 56 cultures for therapeutic TIL; 23 of 26 early cultures (88%) were successfully expanded for in vivo therapy. It took a mean of 78.5 ± 25.4 days to grow sufficient TIL for treatment. Therapy included cyclophosphamide (1 g/m²) on day 1, followed by a 96‐hour continuous infusion of IL‐2 (18 × 10⁶ IU/m²/d) on days 2 to 5, and approximately 10¹¹ (mean 1.49 ± 0.93 × 10¹¹) TIL on day 2. Patients who responded received monthly IL‐2 as a 96‐hour infusion. Median patient age was 45 years of age. Sixty‐seven percent of the patients were men. Performance status was 0 to 1 in 77% of patients. Thirty‐four percent of the patients had liver metastases. The usual IL‐2 toxicities were seen. Response rate for 21 patients was 24% (95% confidence interval, 10% to 49%). One complete response was achieved with cells 98% CD4+; four partial responses were achieved with cells 80%, 94%, 98%, and 98% CD8+, respectively. Four of eight patients who received TIL, which had never been stimulated with OKT3, had tumor response. The authors conclude that a treatment plan for IL‐2/TIL is technically difficult, costly, and effective for only a minority of patients. Overall, clinical results are not clearly superior to those obtained with other IL‐2 regimens.