1. Disabling Immune Tolerance by Programmed Death-1 Blockade With Pidilizumab After Autologous Hematopoietic Stem-Cell Transplantation for Diffuse Large B-Cell Lymphoma: Results of an International Phase II Trial
- Author
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Armand, Philippe, Nagler, Arnon, Weller, Edie A, Devine, Steven M, Avigan, David E, Chen, Yi-Bin, Kaminski, Mark S, Holland, H Kent, Winter, Jane N, Mason, James R, Fay, Joseph W, Rizzieri, David A, Hosing, Chitra M, Ball, Edward D, Uberti, Joseph P, Lazarus, Hillard M, Mapara, Markus Y, Gregory, Stephanie A, Timmerman, John M, Andorsky, David, Or, Reuven, Waller, Edmund K, Rotem-Yehudar, Rinat, and Gordon, Leo I
- Subjects
Rare Diseases ,Cancer ,Hematology ,Biotechnology ,Transplantation ,Clinical Research ,Stem Cell Research ,Lymphoma ,Prevention ,Evaluation of treatments and therapeutic interventions ,6.2 Cellular and gene therapies ,Adult ,Aged ,Aged ,80 and over ,Antibodies ,Monoclonal ,Chile ,Combined Modality Therapy ,Disease-Free Survival ,Drug Administration Schedule ,Fatigue ,Female ,Hematopoietic Stem Cell Transplantation ,Humans ,Immune Tolerance ,India ,Israel ,Lymphocyte Count ,Lymphoma ,Large B-Cell ,Diffuse ,Male ,Middle Aged ,Neutropenia ,Programmed Cell Death 1 Receptor ,Transplantation ,Autologous ,Treatment Outcome ,United States ,Young Adult ,Clinical Sciences ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
PurposeThe Programmed Death-1 (PD-1) immune checkpoint pathway may be usurped by tumors, including diffuse large B-cell lymphoma (DLBCL), to evade immune surveillance. The reconstituting immune landscape after autologous hematopoietic stem-cell transplantation (AHSCT) may be particularly favorable for breaking immune tolerance through PD-1 blockade.Patients and methodsWe conducted an international phase II study of pidilizumab, an anti-PD-1 monoclonal antibody, in patients with DLBCL undergoing AHSCT, with correlative studies of lymphocyte subsets. Patients received three doses of pidilizumab beginning 1 to 3 months after AHSCT.ResultsSixty-six eligible patients were treated. Toxicity was mild. At 16 months after the first treatment, progression-free survival (PFS) was 0.72 (90% CI, 0.60 to 0.82), meeting the primary end point. Among the 24 high-risk patients who remained positive on positron emission tomography after salvage chemotherapy, the 16-month PFS was 0.70 (90% CI, 0.51 to 0.82). Among the 35 patients with measurable disease after AHSCT, the overall response rate after pidilizumab treatment was 51%. Treatment was associated with increases in circulating lymphocyte subsets including PD-L1E-bearing lymphocytes, suggesting an on-target in vivo effect of pidilizumab.ConclusionThis is the first demonstration of clinical activity of PD-1 blockade in DLBCL. Given these results, PD-1 blockade after AHSCT using pidilizumab may represent a promising therapeutic strategy in this disease.
- Published
- 2013