Randomized, prospective evaluation comparing intensity of lymphodepletion before adoptive transfer of tumor-infiltrating lymphocytes for patients with metastatic melanoma

Stephanie L. Goff, Mark E. Dudley, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, Daniel A. Zlott, James C. Yang, Richard M. Sherry, Udai S. Kammula, Christopher A. Klebanoff, Marybeth S. Hughes, Nicholas P. Restifo, Michelle M. Langhan, Thomas E. Shelton, Lily Lu, Mei Li M Kwong, Sadia Ilyas, Nicholas D. Klemen, Eden C. Payabyab & 5 others Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, Steven A. Rosenberg

Research output: Contribution to journalArticle

Abstract

Purpose: Adoptive cell transfer, the infusion of large numbers of activated autologous lymphocytes, can mediate objective tumor regression in a majority of patients with metastatic melanoma (52 of 93; 56%). Addition and intensification of total body irradiation (TBI) to the preparative lymphodepleting chemotherapy regimen in sequential trials improved objective partial and complete response (CR) rates. Here, we evaluated the importance of adding TBI to the adoptive transfer of tumorinfiltrating lymphocytes (TIL) in a randomized fashion. Patients and Methods: A total of 101 patients with metastatic melanoma, including 76 patients with M1c disease, were randomly assigned to receive nonmyeloablative chemotherapy with or without 1,200 cGy TBI before transfer of tumor-infiltrating lymphcytes. Primary end points were CR rate (as defined by Response Evaluation Criteria in Solid Tumors v1.0) and overall survival (OS). Clinical and laboratory data were analyzed for correlates of response. Results: CR rates were 24% in both groups (12 of 50 v 12 of 51), and OS was also similar (median OS, 38.2 v 36.6 months; hazard ratio, 1.11; 95% CI, 0.65 to 1.91; P = .71). Thrombotic microangiopathy was an adverse event unique to the TBI arm and occurred in 13 of 48 treated patients. With a median potential follow-up of 40.9 months, only one of 24 patients who achieved a CR recurred. Conclusion: Adoptive cell transfer can mediate durable complete regressions in 24% of patients with metastatic melanoma, with median survival > 3 years. Results were similar using chemotherapy preparative regimens with or without addition of TBI.

Original languageEnglish (US)
Pages (from-to)2389-2397
Number of pages9
JournalJournal of Clinical Oncology
Volume34
Issue number20
DOIs
StatePublished - Jul 10 2016
Externally publishedYes

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Tumor-Infiltrating Lymphocytes
Adoptive Transfer
Melanoma
Whole-Body Irradiation
Survival
Drug Therapy
Lymphocytes
Thrombotic Microangiopathies
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Randomized, prospective evaluation comparing intensity of lymphodepletion before adoptive transfer of tumor-infiltrating lymphocytes for patients with metastatic melanoma. / Goff, Stephanie L.; Dudley, Mark E.; Citrin, Deborah E.; Somerville, Robert P.; Wunderlich, John R.; Danforth, David N.; Zlott, Daniel A.; Yang, James C.; Sherry, Richard M.; Kammula, Udai S.; Klebanoff, Christopher A.; Hughes, Marybeth S.; Restifo, Nicholas P.; Langhan, Michelle M.; Shelton, Thomas E.; Lu, Lily; Kwong, Mei Li M; Ilyas, Sadia; Klemen, Nicholas D.; Payabyab, Eden C.; Morton, Kathleen E.; Toomey, Mary Ann; Steinberg, Seth M.; White, Donald E.; Rosenberg, Steven A.

In: Journal of Clinical Oncology, Vol. 34, No. 20, 10.07.2016, p. 2389-2397.

Research output: Contribution to journalArticle

Goff, SL, Dudley, ME, Citrin, DE, Somerville, RP, Wunderlich, JR, Danforth, DN, Zlott, DA, Yang, JC, Sherry, RM, Kammula, US, Klebanoff, CA, Hughes, MS, Restifo, NP, Langhan, MM, Shelton, TE, Lu, L, Kwong, MLM, Ilyas, S, Klemen, ND, Payabyab, EC, Morton, KE, Toomey, MA, Steinberg, SM, White, DE & Rosenberg, SA 2016, 'Randomized, prospective evaluation comparing intensity of lymphodepletion before adoptive transfer of tumor-infiltrating lymphocytes for patients with metastatic melanoma', Journal of Clinical Oncology, vol. 34, no. 20, pp. 2389-2397. https://doi.org/10.1200/JCO.2016.66.7220
Goff, Stephanie L. ; Dudley, Mark E. ; Citrin, Deborah E. ; Somerville, Robert P. ; Wunderlich, John R. ; Danforth, David N. ; Zlott, Daniel A. ; Yang, James C. ; Sherry, Richard M. ; Kammula, Udai S. ; Klebanoff, Christopher A. ; Hughes, Marybeth S. ; Restifo, Nicholas P. ; Langhan, Michelle M. ; Shelton, Thomas E. ; Lu, Lily ; Kwong, Mei Li M ; Ilyas, Sadia ; Klemen, Nicholas D. ; Payabyab, Eden C. ; Morton, Kathleen E. ; Toomey, Mary Ann ; Steinberg, Seth M. ; White, Donald E. ; Rosenberg, Steven A. / Randomized, prospective evaluation comparing intensity of lymphodepletion before adoptive transfer of tumor-infiltrating lymphocytes for patients with metastatic melanoma. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 20. pp. 2389-2397.
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abstract = "Purpose: Adoptive cell transfer, the infusion of large numbers of activated autologous lymphocytes, can mediate objective tumor regression in a majority of patients with metastatic melanoma (52 of 93; 56{\%}). Addition and intensification of total body irradiation (TBI) to the preparative lymphodepleting chemotherapy regimen in sequential trials improved objective partial and complete response (CR) rates. Here, we evaluated the importance of adding TBI to the adoptive transfer of tumorinfiltrating lymphocytes (TIL) in a randomized fashion. Patients and Methods: A total of 101 patients with metastatic melanoma, including 76 patients with M1c disease, were randomly assigned to receive nonmyeloablative chemotherapy with or without 1,200 cGy TBI before transfer of tumor-infiltrating lymphcytes. Primary end points were CR rate (as defined by Response Evaluation Criteria in Solid Tumors v1.0) and overall survival (OS). Clinical and laboratory data were analyzed for correlates of response. Results: CR rates were 24{\%} in both groups (12 of 50 v 12 of 51), and OS was also similar (median OS, 38.2 v 36.6 months; hazard ratio, 1.11; 95{\%} CI, 0.65 to 1.91; P = .71). Thrombotic microangiopathy was an adverse event unique to the TBI arm and occurred in 13 of 48 treated patients. With a median potential follow-up of 40.9 months, only one of 24 patients who achieved a CR recurred. Conclusion: Adoptive cell transfer can mediate durable complete regressions in 24{\%} of patients with metastatic melanoma, with median survival > 3 years. Results were similar using chemotherapy preparative regimens with or without addition of TBI.",
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TY - JOUR

T1 - Randomized, prospective evaluation comparing intensity of lymphodepletion before adoptive transfer of tumor-infiltrating lymphocytes for patients with metastatic melanoma

AU - Goff, Stephanie L.

AU - Dudley, Mark E.

AU - Citrin, Deborah E.

AU - Somerville, Robert P.

AU - Wunderlich, John R.

AU - Danforth, David N.

AU - Zlott, Daniel A.

AU - Yang, James C.

AU - Sherry, Richard M.

AU - Kammula, Udai S.

AU - Klebanoff, Christopher A.

AU - Hughes, Marybeth S.

AU - Restifo, Nicholas P.

AU - Langhan, Michelle M.

AU - Shelton, Thomas E.

AU - Lu, Lily

AU - Kwong, Mei Li M

AU - Ilyas, Sadia

AU - Klemen, Nicholas D.

AU - Payabyab, Eden C.

AU - Morton, Kathleen E.

AU - Toomey, Mary Ann

AU - Steinberg, Seth M.

AU - White, Donald E.

AU - Rosenberg, Steven A.

PY - 2016/7/10

Y1 - 2016/7/10

N2 - Purpose: Adoptive cell transfer, the infusion of large numbers of activated autologous lymphocytes, can mediate objective tumor regression in a majority of patients with metastatic melanoma (52 of 93; 56%). Addition and intensification of total body irradiation (TBI) to the preparative lymphodepleting chemotherapy regimen in sequential trials improved objective partial and complete response (CR) rates. Here, we evaluated the importance of adding TBI to the adoptive transfer of tumorinfiltrating lymphocytes (TIL) in a randomized fashion. Patients and Methods: A total of 101 patients with metastatic melanoma, including 76 patients with M1c disease, were randomly assigned to receive nonmyeloablative chemotherapy with or without 1,200 cGy TBI before transfer of tumor-infiltrating lymphcytes. Primary end points were CR rate (as defined by Response Evaluation Criteria in Solid Tumors v1.0) and overall survival (OS). Clinical and laboratory data were analyzed for correlates of response. Results: CR rates were 24% in both groups (12 of 50 v 12 of 51), and OS was also similar (median OS, 38.2 v 36.6 months; hazard ratio, 1.11; 95% CI, 0.65 to 1.91; P = .71). Thrombotic microangiopathy was an adverse event unique to the TBI arm and occurred in 13 of 48 treated patients. With a median potential follow-up of 40.9 months, only one of 24 patients who achieved a CR recurred. Conclusion: Adoptive cell transfer can mediate durable complete regressions in 24% of patients with metastatic melanoma, with median survival > 3 years. Results were similar using chemotherapy preparative regimens with or without addition of TBI.

AB - Purpose: Adoptive cell transfer, the infusion of large numbers of activated autologous lymphocytes, can mediate objective tumor regression in a majority of patients with metastatic melanoma (52 of 93; 56%). Addition and intensification of total body irradiation (TBI) to the preparative lymphodepleting chemotherapy regimen in sequential trials improved objective partial and complete response (CR) rates. Here, we evaluated the importance of adding TBI to the adoptive transfer of tumorinfiltrating lymphocytes (TIL) in a randomized fashion. Patients and Methods: A total of 101 patients with metastatic melanoma, including 76 patients with M1c disease, were randomly assigned to receive nonmyeloablative chemotherapy with or without 1,200 cGy TBI before transfer of tumor-infiltrating lymphcytes. Primary end points were CR rate (as defined by Response Evaluation Criteria in Solid Tumors v1.0) and overall survival (OS). Clinical and laboratory data were analyzed for correlates of response. Results: CR rates were 24% in both groups (12 of 50 v 12 of 51), and OS was also similar (median OS, 38.2 v 36.6 months; hazard ratio, 1.11; 95% CI, 0.65 to 1.91; P = .71). Thrombotic microangiopathy was an adverse event unique to the TBI arm and occurred in 13 of 48 treated patients. With a median potential follow-up of 40.9 months, only one of 24 patients who achieved a CR recurred. Conclusion: Adoptive cell transfer can mediate durable complete regressions in 24% of patients with metastatic melanoma, with median survival > 3 years. Results were similar using chemotherapy preparative regimens with or without addition of TBI.

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JO - Journal of Clinical Oncology

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