Randomized, Prospective Evaluation Comparing Intensity of Lymphodepletion Before Adoptive Transfer of Tumor-Infiltrating Lymphocytes for Patients With Metastatic Melanoma

Author:

Goff Stephanie L.1,Dudley Mark E.1,Citrin Deborah E.1,Somerville Robert P.1,Wunderlich John R.1,Danforth David N.1,Zlott Daniel A.1,Yang James C.1,Sherry Richard M.1,Kammula Udai S.1,Klebanoff Christopher A.1,Hughes Marybeth S.1,Restifo Nicholas P.1,Langhan Michelle M.1,Shelton Thomas E.1,Lu Lily1,Kwong Mei Li M.1,Ilyas Sadia1,Klemen Nicholas D.1,Payabyab Eden C.1,Morton Kathleen E.1,Toomey Mary Ann1,Steinberg Seth M.1,White Donald E.1,Rosenberg Steven A.1

Affiliation:

1. Stephanie L. Goff, Deborah E. Citrin, Robert P. Somerville, John R. Wunderlich, David N. Danforth, 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, Kathleen E. Morton, Mary Ann Toomey, Seth M. Steinberg, Donald E. White, and Steven A. Rosenberg, National Cancer Institute, National Institutes of Health; Daniel A. Zlott,...

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 tumor-infiltrating 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.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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