TY - JOUR
T1 - Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma
AU - Dudley, Mark E.
AU - Wunderlich, John R.
AU - Yang, James C.
AU - Sherry, Richard M.
AU - Topalian, Suzanne L.
AU - Restifo, Nicholas P.
AU - Royal, Richard E.
AU - Kammula, Udai
AU - White, Don E.
AU - Mavroukakis, Sharon A.
AU - Rogers, Linda J.
AU - Gracia, Gerald J.
AU - Jones, Stephanie A.
AU - Mangiameli, David P.
AU - Pelletier, Michelle M.
AU - Gea-Banacloche, Juan
AU - Robinson, Michael R.
AU - Berman, David M.
AU - Filie, Armando C.
AU - Abati, Andrea
AU - Rosenberg, Steven A.
PY - 2005
Y1 - 2005
N2 - Purpose: We investigated the combination of lymphodepleting chemotherapy followed by the adoptive transfer of autologous tumor reactive lymphocytes for the treatment of patients with refractory metastatic melanoma. Patients and Methods: Thirty-five patients with metastatic melanoma, all but one with disease refractory to treatment with high-dose interleukin (IL)-2 and many with progressive disease after chemotherapy, underwent lymphodepleting conditioning with two days of cyclophosphamide (60 mg/kg) followed by five days of fludarabine (25 mg/m2). On the day following the final dose of fludarabine, all patients received cell infusion with autologous tumor-reactive, rapidly expanded tumor infiltrating lymphocyte cultures and high-dose IL-2 therapy. Results Eighteen (51%) of 35 treated patients experienced objective clinical responses including three ongoing complete responses and 15 partial responses with a mean duration of 11.5 ± 2.2 months. Sites of regression included metastases to lung, liver, lymph nodes, brain, and cutaneous and subcutaneous tissues. Toxicities of treatment included the expected hematologic toxicities of chemotherapy including neutropenia, thrombocytopenia, and lymphopenia, the transient toxicities of high-dose IL-2 therapy, two patients who developed Pneumocystis pneumonia and one patient who developed an Epstein-Barr virus-related lymphoproliferation. Conclusion: Lymphodepleting chemotherapy followed by the transfer of highly avid antitumor lymphocytes can mediate significant tumor regression in heavily pretreated patients with IL-2 refractory metastatic melanoma.
AB - Purpose: We investigated the combination of lymphodepleting chemotherapy followed by the adoptive transfer of autologous tumor reactive lymphocytes for the treatment of patients with refractory metastatic melanoma. Patients and Methods: Thirty-five patients with metastatic melanoma, all but one with disease refractory to treatment with high-dose interleukin (IL)-2 and many with progressive disease after chemotherapy, underwent lymphodepleting conditioning with two days of cyclophosphamide (60 mg/kg) followed by five days of fludarabine (25 mg/m2). On the day following the final dose of fludarabine, all patients received cell infusion with autologous tumor-reactive, rapidly expanded tumor infiltrating lymphocyte cultures and high-dose IL-2 therapy. Results Eighteen (51%) of 35 treated patients experienced objective clinical responses including three ongoing complete responses and 15 partial responses with a mean duration of 11.5 ± 2.2 months. Sites of regression included metastases to lung, liver, lymph nodes, brain, and cutaneous and subcutaneous tissues. Toxicities of treatment included the expected hematologic toxicities of chemotherapy including neutropenia, thrombocytopenia, and lymphopenia, the transient toxicities of high-dose IL-2 therapy, two patients who developed Pneumocystis pneumonia and one patient who developed an Epstein-Barr virus-related lymphoproliferation. Conclusion: Lymphodepleting chemotherapy followed by the transfer of highly avid antitumor lymphocytes can mediate significant tumor regression in heavily pretreated patients with IL-2 refractory metastatic melanoma.
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U2 - 10.1200/JCO.2005.00.240
DO - 10.1200/JCO.2005.00.240
M3 - Article
C2 - 15800326
AN - SCOPUS:20244366111
SN - 0732-183X
VL - 23
SP - 2346
EP - 2357
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 10
ER -