Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma

Mark E. Dudley, John R. Wunderlich, James C. Yang, Richard M. Sherry, Suzanne Topalian, Nicholas P. Restifo, Richard E. Royal, Udai Kammula, Don E. White, Sharon A. Mavroukakis, Linda J. Rogers, Gerald J. Gracia, Stephanie A. Jones, David P. Mangiameli, Michelle M. Pelletier, Juan Gea-Banacloche, Michael R. Robinson, David M. Berman, Armando C. Filie, Andrea AbatiSteven A. Rosenberg

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2346-2357
Number of pages12
JournalJournal of Clinical Oncology
Volume23
Issue number10
DOIs
StatePublished - 2005
Externally publishedYes

Fingerprint

Adoptive Transfer
Cell- and Tissue-Based Therapy
Melanoma
Drug Therapy
Interleukin-2
Therapeutics
Lymphocytes
Tumor-Infiltrating Lymphocytes
Neoplasms
Lymphopenia
Pneumocystis Pneumonia
Subcutaneous Tissue
Combination Drug Therapy
Neutropenia
Human Herpesvirus 4
Thrombocytopenia
Cyclophosphamide
Lymph Nodes
Neoplasm Metastasis
Lung

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. / Dudley, Mark E.; Wunderlich, John R.; Yang, James C.; Sherry, Richard M.; Topalian, Suzanne; Restifo, Nicholas P.; Royal, Richard E.; Kammula, Udai; White, Don E.; Mavroukakis, Sharon A.; Rogers, Linda J.; Gracia, Gerald J.; Jones, Stephanie A.; Mangiameli, David P.; Pelletier, Michelle M.; Gea-Banacloche, Juan; Robinson, Michael R.; Berman, David M.; Filie, Armando C.; Abati, Andrea; Rosenberg, Steven A.

In: Journal of Clinical Oncology, Vol. 23, No. 10, 2005, p. 2346-2357.

Research output: Contribution to journalArticle

Dudley, ME, Wunderlich, JR, Yang, JC, Sherry, RM, Topalian, S, Restifo, NP, Royal, RE, Kammula, U, White, DE, Mavroukakis, SA, Rogers, LJ, Gracia, GJ, Jones, SA, Mangiameli, DP, Pelletier, MM, Gea-Banacloche, J, Robinson, MR, Berman, DM, Filie, AC, Abati, A & Rosenberg, SA 2005, 'Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma', Journal of Clinical Oncology, vol. 23, no. 10, pp. 2346-2357. https://doi.org/10.1200/JCO.2005.00.240
Dudley, Mark E. ; Wunderlich, John R. ; Yang, James C. ; Sherry, Richard M. ; Topalian, Suzanne ; Restifo, Nicholas P. ; Royal, Richard E. ; Kammula, Udai ; White, Don E. ; Mavroukakis, Sharon A. ; Rogers, Linda J. ; Gracia, Gerald J. ; Jones, Stephanie A. ; Mangiameli, David P. ; Pelletier, Michelle M. ; Gea-Banacloche, Juan ; Robinson, Michael R. ; Berman, David M. ; Filie, Armando C. ; Abati, Andrea ; Rosenberg, Steven A. / Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. In: Journal of Clinical Oncology. 2005 ; Vol. 23, No. 10. pp. 2346-2357.
@article{2874873cde3542f1983cb6327a41bf4d,
title = "Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma",
abstract = "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.",
author = "Dudley, {Mark E.} and Wunderlich, {John R.} and Yang, {James C.} and Sherry, {Richard M.} and Suzanne Topalian and Restifo, {Nicholas P.} and Royal, {Richard E.} and Udai Kammula and White, {Don E.} and Mavroukakis, {Sharon A.} and Rogers, {Linda J.} and Gracia, {Gerald J.} and Jones, {Stephanie A.} and Mangiameli, {David P.} and Pelletier, {Michelle M.} and Juan Gea-Banacloche and Robinson, {Michael R.} and Berman, {David M.} and Filie, {Armando C.} and Andrea Abati and Rosenberg, {Steven A.}",
year = "2005",
doi = "10.1200/JCO.2005.00.240",
language = "English (US)",
volume = "23",
pages = "2346--2357",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "10",

}

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

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.

UR - http://www.scopus.com/inward/record.url?scp=20244366111&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20244366111&partnerID=8YFLogxK

U2 - 10.1200/JCO.2005.00.240

DO - 10.1200/JCO.2005.00.240

M3 - Article

C2 - 15800326

AN - SCOPUS:20244366111

VL - 23

SP - 2346

EP - 2357

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 10

ER -