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Durable Complete Responses in Heavily Pretreated Patients with Metastatic Melanoma Using T-Cell Transfer Immunotherapy

ROSENBERG, Steven A ; YANG, James C ; MORTON, Kathleen E ; LAURENCOT, Carolyn M ; STEINBERG, Seth M ; WHITE, Donald E ; DUDLEY, Mark E ; SHERRY, Richard M ; KAMMULA, Udai S ; HUGHES, Marybeth S ; PHAN, Giao Q ; CITRIN, Deborah E ; RESTIFO, Nicholas P ; ROBBINS, Paul F ; WUNDERLICH, John R

Clinical cancer research, 2011-07, Vol.17 (13), p.4550-4557 [Peer Reviewed Journal]

Philadelphia, PA: American Association for Cancer Research

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Title:
Durable Complete Responses in Heavily Pretreated Patients with Metastatic Melanoma Using T-Cell Transfer Immunotherapy
Author: ROSENBERG, Steven A ; YANG, James C ; MORTON, Kathleen E ; LAURENCOT, Carolyn M ; STEINBERG, Seth M ; WHITE, Donald E ; DUDLEY, Mark E ; SHERRY, Richard M ; KAMMULA, Udai S ; HUGHES, Marybeth S ; PHAN, Giao Q ; CITRIN, Deborah E ; RESTIFO, Nicholas P ; ROBBINS, Paul F ; WUNDERLICH, John R
Subjects: Adolescent ; Adult ; Aged ; Antineoplastic agents ; Biological and medical sciences ; Combined Modality Therapy ; Dermatology ; Female ; Humans ; Immunotherapy, Adoptive ; Lymphocyte Count ; Lymphocytes, Tumor-Infiltrating - immunology ; Male ; Medical sciences ; Melanoma - mortality ; Melanoma - pathology ; Melanoma - therapy ; Middle Aged ; Pharmacology. Drug treatments ; Survival Analysis ; Telomere - genetics ; Treatment Outcome ; Tumors of the skin and soft tissue. Premalignant lesions ; Young Adult
Is Part Of: Clinical cancer research, 2011-07, Vol.17 (13), p.4550-4557
Notes: ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
Description: 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. 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. 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 P(2) < 0.001). 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.
Publisher: Philadelphia, PA: American Association for Cancer Research
Language: English

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Durable Complete Responses in Heavily Pretreated Patients with Metastatic Melanoma Using T-Cell Transfer Immunotherapy

ROSENBERG, Steven A ; YANG, James C ; MORTON, Kathleen E ; LAURENCOT, Carolyn M ; STEINBERG, Seth M ; WHITE, Donald E ; DUDLEY, Mark E ; SHERRY, Richard M ; KAMMULA, Udai S ; HUGHES, Marybeth S ; PHAN, Giao Q ; CITRIN, Deborah E ; RESTIFO, Nicholas P ; ROBBINS, Paul F ; WUNDERLICH, John R

Philadelphia, PA: American Association for Cancer Research

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