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

Publication ,  Journal Article
Dudley, ME; Yang, JC; Sherry, R; Hughes, MS; Royal, R; Kammula, U; Robbins, PF; Huang, J; Citrin, DE; Leitman, SF; Wunderlich, J; Restifo, NP ...
Published in: J Clin Oncol
November 10, 2008

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.

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Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

November 10, 2008

Volume

26

Issue

32

Start / End Page

5233 / 5239

Location

United States

Related Subject Headings

  • Vidarabine
  • Treatment Outcome
  • Time Factors
  • Radiotherapy, Adjuvant
  • Radiotherapy Dosage
  • Pilot Projects
  • Oncology & Carcinogenesis
  • Neoplasm Metastasis
  • Neoadjuvant Therapy
  • Myeloablative Agonists
 

Citation

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Dudley, M. E., Yang, J. C., Sherry, R., Hughes, M. S., Royal, R., Kammula, U., … Rosenberg, S. A. (2008). Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol, 26(32), 5233–5239. https://doi.org/10.1200/JCO.2008.16.5449
Dudley, Mark E., James C. Yang, Richard Sherry, Marybeth S. Hughes, Richard Royal, Udai Kammula, Paul F. Robbins, et al. “Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens.J Clin Oncol 26, no. 32 (November 10, 2008): 5233–39. https://doi.org/10.1200/JCO.2008.16.5449.
Dudley ME, Yang JC, Sherry R, Hughes MS, Royal R, Kammula U, et al. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol. 2008 Nov 10;26(32):5233–9.
Dudley, Mark E., et al. “Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens.J Clin Oncol, vol. 26, no. 32, Nov. 2008, pp. 5233–39. Pubmed, doi:10.1200/JCO.2008.16.5449.
Dudley ME, Yang JC, Sherry R, Hughes MS, Royal R, Kammula U, Robbins PF, Huang J, Citrin DE, Leitman SF, Wunderlich J, Restifo NP, Thomasian A, Downey SG, Smith FO, Klapper J, Morton K, Laurencot C, White DE, Rosenberg SA. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol. 2008 Nov 10;26(32):5233–5239.

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

November 10, 2008

Volume

26

Issue

32

Start / End Page

5233 / 5239

Location

United States

Related Subject Headings

  • Vidarabine
  • Treatment Outcome
  • Time Factors
  • Radiotherapy, Adjuvant
  • Radiotherapy Dosage
  • Pilot Projects
  • Oncology & Carcinogenesis
  • Neoplasm Metastasis
  • Neoadjuvant Therapy
  • Myeloablative Agonists