Adoptive cell therapy for patients with metastatic melanoma: Evaluation of intensive myeloablative chemoradiation preparative regimens

Mark E. Dudley, James C. Yang, Richard Sherry, Marybeth S. Hughes, Richard Royal, Udai Kammula, Paul F. Robbins, Jian Ping Huang, Deborah E. Citrin, Susan F. Leitman, John Wunderlich, Nicholas P. Restifo, Armen Thomasian, Stephanie G. Downey, Franz O. Smith, Jacob Klapper, Kathleen Morton, Carolyn Laurencot, Donald E. White, Steven A. Rosenberg

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: The two approved treatments for patients with metastatic melanoma, interleukin (IL)-2 and dacarbazine, mediate objective response rates of 12% to 15%. We previously reported that adoptive cell therapy (ACT) with autologous antitumor lymphocytes in lymphodepleted hosts mediated objective responses in 51% of 35 patients. Here, we update that study and evaluate the safety and efficacy of two increased-intensity myeloablative lymphodepleting regimens. Patients and Methods: We performed two additional sequential trials of ACT with autologous tumor-infiltrating lymphocytes (TIL) in patients with metastatic melanoma. Increasing intensity of host preparative lymphodepletion consisting of cyclophosphamide and fludarabine with either 2 (25 patients) or 12 Gy (25 patients) of total-body irradiation (TBI) was administered before cell transfer. Objective response rates by Response Evaluation Criteria in Solid Tumors (RECIST) and survival were evaluated. Immunologic correlates of effective treatment were studied. Results: Although nonmyeloablative chemotherapy alone showed an objective response rate of 49%, when 2 or 12 Gy of TBI was added, the response rates were 52% and 72% respectively. Responses were seen in all visceral sites including brain. There was one treatment-related death in the 93 patients. Host lymphodepletion was associated with increased serum levels of the lymphocyte homeostatic cytokines IL-7 and IL-15. Objective responses were correlated with the telomere length of the transferred cells. Conclusion: Host lymphodepletion followed by autologous TIL transfer and IL-2 results in objective response rates of 50% to 70% in patients with metastatic melanoma refractory to standard therapies.

Original languageEnglish (US)
Pages (from-to)5233-5239
Number of pages7
JournalJournal of Clinical Oncology
Volume26
Issue number32
DOIs
StatePublished - Nov 10 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Adoptive cell therapy for patients with metastatic melanoma: Evaluation of intensive myeloablative chemoradiation preparative regimens'. Together they form a unique fingerprint.

Cite this