UNASSIGNED: 2507 Background: We have previously demonstrated that administration of a recombinant @entity1199 /diphtheria toxin conjugate (DAB/ @entity1199 ; ONTAK; Denileukin Diftitox) to @entity320 @entity1 transiently depletes T cells, including regulatory T cells, and promotes the expansion of @entity320 -specific effector T cells. The goals of this study were to examine the effects of DAB/ @entity1199 on additional lymphocyte subsets, monocytes, neutrophils and @entity2841 and assess clinical efficacy in stage IV @entity320 @entity1 . METHODS: We first administered DAB/ @entity1199 (12   g/kg; daily x 4 days; 21 day cycles) to 10 stage IV @entity320 @entity1 and measured effects on lymphocyte subsets and myeloid-derived cells by flow cytometry and serum @entity2841 by ELISA. We then determined objective response rates (using FDG-PET and CT) and one year survival in a total of 60 @entity1 given DAB/ @entity1199 . RESULTS: We found that DAB/ @entity1199 transiently depleted total lymphocytes, NK, B and T cells and conversely increased monocyte and neutrophil counts with a coincident increase in serum @entity2841 (baseline, 0.54    0.27; day 7, 1.38    0.19 pg/ml, p value <0.01). 16.7% of @entity1 had partial responses, 5% stable disease and 15% mixed responses (83% of these @entity1 were pre-treated with 1-5 prior systemic regimens). However, 45.5% of the chemo/immune-na  ve @entity1 , the majority with visceral metastases (stage M1C), had partial responses including delayed @entity5 regressions and durable stability of residual metastases, indicating a potential immunotherapeutic mechanism. While the total 1 year survival was 40    6.2%, the partial responder 1 year survival was 80   11.9% ( p value < 0.001). CONCLUSIONS: Taken together, these data indicate that DAB/ @entity1199 demonstrates significant clinical activity in chemo/immune-na  ve stage IV @entity320 @entity1 that may be due to a combination of transient depletion of multiple lymphocyte subsets including regulatory T cells, stimulation of @entity2841 secretion and myeloid cell expansion. The high partial response rate in na  ve @entity1 coupled to the improved 1 year survival in responders supports the conduct of additional trials of DAB/ @entity1199 for the treatment of @entity320 .

Effect of denileukin diftitox on serum @entity2841 and clinical responses in stage IV XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity1199 :: ('3558', 'Gene') :: ['IL2', 'interleukin 2'] @entity2841 :: ('1437', 'Gene') :: ['GM-CSF'] @entity320 :: ('MESH:D008545', 'Disease') :: ['melanoma', 'metastatic melanoma']
@entity320 :: (MESH:D008545,Disease) :: ['melanoma']
