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
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, Clinical Center, National Institutes of Health, Bethesda, MD; and Mark E. Dudley, Novartis Institutes for BioMedical Research, Cambridge, MA.
J Clin Oncol. 2016 Jul 10;34(20):2389-97. doi: 10.1200/JCO.2016.66.7220. Epub 2016 May 23.
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.
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.
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.
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.
过继性细胞转移，即输注大量活化的自体淋巴细胞，可使大多数转移性黑色素瘤患者出现客观的肿瘤消退（93例中的52例；56%）。在序贯试验中，在预处理的淋巴细胞清除化疗方案中添加并强化全身照射（TBI）可提高客观部分缓解和完全缓解（CR）率。在此，我们以随机方式评估了在肿瘤浸润淋巴细胞（TIL）过继性转移中添加TBI的重要性。
总共101例转移性黑色素瘤患者，包括76例M1c期疾病患者，被随机分配在肿瘤浸润淋巴细胞转移前接受非清髓性化疗，化疗方案中含或不含1200 cGy的TBI。主要终点为CR率（按照实体瘤疗效评价标准第1.0版定义）和总生存期（OS）。分析临床和实验室数据以寻找反应的相关因素。
两组的CR率均为24%（50例中的12例对51例中的12例），OS也相似（中位OS，38.2个月对36.6个月；风险比，1.11；95%CI，0.65至1.91；P = 0.71）。血栓性微血管病是TBI组特有的不良事件，在48例接受治疗的患者中有13例发生。中位潜在随访时间为40.9个月时，24例达到CR的患者中只有1例复发。
过继性细胞转移可使24%的转移性黑色素瘤患者实现持久的完全缓解，中位生存期>3年。使用含或不含TBI的化疗预处理方案的结果相似。
