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Blood, 12 February 2009, Vol. 113, No. 7, pp. 1581-1588. Prepublished online as a Blood First Edition Paper on October 30, 2008; DOI 10.1182/blood-2008-07-168468. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-07-168468v1 113/7/1581    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bashey, A. Articles by Ball, E. D. Search for Related Content PubMed PubMed Citation Articles by Bashey, A. Articles by Ball, E. D. Related Collections Transplantation Free Research Articles Myeloid Neoplasia Lymphoid Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell transplantation Asad Bashey1,2, Bridget Medina1, Sue Corringham1, Mildred Pasek2, Ewa Carrier1, Linda Vrooman2, Israel Lowy3, Scott R. Solomon2, Lawrence E. Morris2, H. Kent Holland2, James R. Mason4, Edwin P. Alyea5, Robert J. Soiffer5, and Edward D. Ball1 1 Division of Blood and Marrow Transplantation, University of California, San Diego Moores Cancer Center, La Jolla; 2 Blood and Marrow Transplant Group of Georgia at Northside Hospital, Atlanta; 3 Medarex, Bloomsbury, NJ; 4 BMT, Scripps Clinic, La Jolla, CA; and 5 Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA Relapse of malignancy after allogeneic hematopoietic cell transplantation (allo-HCT) remains a therapeutic challenge. Blockade of the CTLA4 molecule can effectively augment antitumor immunity mediated by autologous effector T cells. We have assessed the safety and preliminary efficacy of a neutralizing, human anti-CTLA4 monoclonal antibody, ipilimumab, in stimulating the graft-versus-malignancy (GVM) effect after allo-HCT. Twenty-nine patients with malignancies that were recurrent or progressive after allo-HCT, received ipilimumab as a single infusion at dose cohorts between 0.1 and 3.0 mg/kg. Dose-limiting toxicity was not encountered, and ipilimumab did not induce graft-versus-host disease (GVHD) or graft rejection. Organ-specific immune adverse events (IAE) were seen in 4 patients (grade 3 arthritis, grade 2 hyperthyroidism, recurrent grade 4 pneumonitis). Three patients with lymphoid malignancy developed objective disease responses following ipilimumab: complete remission (CR) in 2 patients with Hodgkin disease and partial remission (PR) in a patient with refractory mantle cell lymphoma. At the 3.0 mg/kg dose, active serum concentrations of ipilimumab were maintained for more than 30 days after a single infusion. Ipilimumab, as administered in this clinical trial, does not induce or exacerbate clinical GVHD, but may cause organ-specific IAE and regression of malignancy. This study is registered at http://clinicaltrials.gov under NCI protocol ID P6082. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Q. Zhou, C. Bucher, M. E. Munger, S. L. Highfill, J. Tolar, D. H. Munn, B. L. Levine, M. Riddle, C. H. June, D. A. Vallera, et al. Depletion of endogenous tumor-associated regulatory T cells improves the efficacy of adoptive cytotoxic T-cell immunotherapy in murine acute myeloid leukemia Blood, October 29, 2009; 114(18): 3793 - 3802. [Abstract] [Full Text] [PDF] S. M. Ansell, S. A. Hurvitz, P. A. Koenig, B. R. LaPlant, B. F. Kabat, D. Fernando, T. M. Habermann, D. J. Inwards, M. Verma, R. Yamada, et al. Phase I Study of Ipilimumab, an Anti-CTLA-4 Monoclonal Antibody, in Patients with Relapsed and Refractory B-Cell Non-Hodgkin Lymphoma Clin. Cancer Res., October 15, 2009; 15(20): 6446 - 6453. [Abstract] [Full Text] [PDF]

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