PATTERNS OF RELAPSE AND RESPONSE TO RETREATMENT IN PATIENTS WITH METASTATIC MELANOMA OR RENAL-CELL CARCINOMA WHO RESPONDED TO INTERLEUKIN-2-BASED IMMUNOTHERAPY

PURPOSE The purpose of this study was to examine the pattern of relaps e and the treatment of relapse with either surgery or repeat immunothe rapy in patients with metastatic melanoma or renal cell carcinoma who had previously responded to interleukin-2-based therapy. PATIENTS AND METHODS Over a 10-year period 1051 patients with metastatic melanoma o r renal cell carcinoma were treated with interleukin-2-based immunothe rapy at a single institution. One hundred fifty-nine patients who rela psed after an initial partial response or complete response to interle ukin-2-based immunotherapy formed the study population for this retros pective review. Medical records, physical examination forms, and relev ant radiographs were reviewed to determine response, relapse site(s), and response to treatment for relapse. RESULTS Relapse after an initia l response to interleukin-2-based therapy occurred in 84 (80%) of 105 patients with metastatic melanoma and in 75 (70%) of 107 patients with metastatic renal cell carcinoma Relapse after an initial partial resp onse involved 71 (97%) of 73 patients with metastatic melanoma and 55 (86%) of 64 patients with metastatic renal cell carcinoma. The initial site(s) of relapse after a partial response involved a new site(s), o ld site(s), or both old and new sites with relatively even distributio n. Relapse after an initial complete response occurred in 13 (41%) of 32 patients with metastatic melanoma and in 20 (47%) of 43 completely responding patients with metastatic renal cell carcinoma Surprisingly, the initial site of relapse after a complete response involved only n ew sites of disease in 70% of patients. Retreatment of relapses with t he same interleukin-2-based therapy originally used was effective in o nly one (2%) of 54 selected patients, but a different interleukin-2-ba sed therapy in 35 patients resulted in five responders (a 14% secondar y response rate). Most re-responders, however, responded to treatment with tumor-infiltrating lymphocytes and interleukin-2, and only one of 20 patients responded to retreatment with interleukin-2 alone. Surgic al metastasectomy with therapeutic intent in 25 selected melanoma pati ents and in 31 selected renal cell cancer patients resulted in a 2-yea r progression-free survival of 18% in patients with metastatic melanom a and 37% in patients with metastatic renal cell carcinoma. DISCUSSION In patients with metastatic melanoma or renal cell carcinoma, tumor r elapse was common after a partial response to an interleukin-2-based t herapy and included previously identified sites of disease in most pat ients. Relapse after a complete response was less frequent and involve d only new sites in a majority of patients. In selected patients who r elapsed, repeat treatment with the same interleukin-2-based therapy th at provided the initial response was rarely effective. However, with a different interleukin-2-based therapy, usually using tumor-infiltrati ng lymphocytes, repeat treatment induced secondary responses in some p atients. In addition, salvage metastasectomy resulted in durable progr ession-free survival in selected patients.