Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy

SA Rosenberg, JC Yang, RM Sherry, US Kammula… - Clinical cancer …, 2011 - AACR
SA Rosenberg, JC Yang, RM Sherry, US Kammula, MS Hughes, GQ Phan, DE Citrin…
Clinical cancer research, 2011AACR
Purpose: Most treatments for patients with metastatic melanoma have a low rate of complete
regression and thus overall survival in these patients is poor. We investigated the ability of
adoptive cell transfer utilizing autologous tumor-infiltrating lymphocytes (TIL) to mediate
durable complete regressions in heavily pretreated patients with metastatic melanoma.
Experimental Design: Ninety-three patients with measurable metastatic melanoma were
treated with the adoptive transfer of autologous TILs administered in conjunction with …
Abstract
Purpose: Most treatments for patients with metastatic melanoma have a low rate of complete regression and thus overall survival in these patients is poor. We investigated the ability of adoptive cell transfer utilizing autologous tumor-infiltrating lymphocytes (TIL) to mediate durable complete regressions in heavily pretreated patients with metastatic melanoma.
Experimental Design: Ninety-three patients with measurable metastatic melanoma were treated with the adoptive transfer of autologous TILs administered in conjunction with interleukin-2 following a lymphodepleting preparative regimen on three sequential clinical trials. Ninety-five percent of these patients had progressive disease following a prior systemic treatment. Median potential follow-up was 62 months.
Results: Objective response rates by Response Evaluation Criteria in Solid Tumors (RECIST) in the 3 trials using lymphodepleting preparative regimens (chemotherapy alone or with 2 or 12 Gy irradiation) were 49%, 52%, and 72%, respectively. Twenty of the 93 patients (22%) achieved a complete tumor regression, and 19 have ongoing complete regressions beyond 3 years. The actuarial 3- and 5-year survival rates for the entire group were 36% and 29%, respectively, but for the 20 complete responders were 100% and 93%. The likelihood of achieving a complete response was similar regardless of prior therapy. Factors associated with objective response included longer telomeres of the infused cells, the number of CD8+CD27+ cells infused, and the persistence of the infused cells in the circulation at 1 month (all P2 < 0.001).
Conclusions: Cell transfer therapy with autologous TILs can mediate durable complete responses in patients with metastatic melanoma and has similar efficacy irrespective of prior treatment. Clin Cancer Res; 17(13); 4550–7. ©2011 AACR.
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