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

Steven A. Rosenberg, James C. Yang, Richard M. Sherry, Udai S. Kammula, Marybeth S. Hughes, Giao Q. Phan, Deborah E. Citrin, Nicholas P. Restifo, Paul F. Robbins, John R. Wunderlich, Kathleen E. Morton, Carolyn M. Laurencot, Seth M. Steinberg, Donald E. White, Mark E. Dudley

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)4550-4557
Number of pages8
JournalClinical Cancer Research
Volume17
Issue number13
DOIs
StatePublished - Jul 1 2011
Externally publishedYes

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Immunotherapy
Melanoma
T-Lymphocytes
Adoptive Transfer
Tumor-Infiltrating Lymphocytes
Telomere
Therapeutics
Cell- and Tissue-Based Therapy
Interleukin-2
Research Design
Survival Rate
Cell Count
Clinical Trials
Drug Therapy
Survival
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Rosenberg, S. A., Yang, J. C., Sherry, R. M., Kammula, U. S., Hughes, M. S., Phan, G. Q., ... Dudley, M. E. (2011). Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clinical Cancer Research, 17(13), 4550-4557. https://doi.org/10.1158/1078-0432.CCR-11-0116

Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. / Rosenberg, Steven A.; Yang, James C.; Sherry, Richard M.; Kammula, Udai S.; Hughes, Marybeth S.; Phan, Giao Q.; Citrin, Deborah E.; Restifo, Nicholas P.; Robbins, Paul F.; Wunderlich, John R.; Morton, Kathleen E.; Laurencot, Carolyn M.; Steinberg, Seth M.; White, Donald E.; Dudley, Mark E.

In: Clinical Cancer Research, Vol. 17, No. 13, 01.07.2011, p. 4550-4557.

Research output: Contribution to journalArticle

Rosenberg, SA, Yang, JC, Sherry, RM, Kammula, US, Hughes, MS, Phan, GQ, Citrin, DE, Restifo, NP, Robbins, PF, Wunderlich, JR, Morton, KE, Laurencot, CM, Steinberg, SM, White, DE & Dudley, ME 2011, 'Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy', Clinical Cancer Research, vol. 17, no. 13, pp. 4550-4557. https://doi.org/10.1158/1078-0432.CCR-11-0116
Rosenberg, Steven A. ; Yang, James C. ; Sherry, Richard M. ; Kammula, Udai S. ; Hughes, Marybeth S. ; Phan, Giao Q. ; Citrin, Deborah E. ; Restifo, Nicholas P. ; Robbins, Paul F. ; Wunderlich, John R. ; Morton, Kathleen E. ; Laurencot, Carolyn M. ; Steinberg, Seth M. ; White, Donald E. ; Dudley, Mark E. / Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 13. pp. 4550-4557.
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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.",
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T1 - Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy

AU - Rosenberg, Steven A.

AU - Yang, James C.

AU - Sherry, Richard M.

AU - Kammula, Udai S.

AU - Hughes, Marybeth S.

AU - Phan, Giao Q.

AU - Citrin, Deborah E.

AU - Restifo, Nicholas P.

AU - Robbins, Paul F.

AU - Wunderlich, John R.

AU - Morton, Kathleen E.

AU - Laurencot, Carolyn M.

AU - Steinberg, Seth M.

AU - White, Donald E.

AU - Dudley, Mark E.

PY - 2011/7/1

Y1 - 2011/7/1

N2 - 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.

AB - 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.

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