CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell transplantation

Blood. 2009 Feb 12;113(7):1581-8. doi: 10.1182/blood-2008-07-168468. Epub 2008 Oct 30.


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.

Trial registration: ClinicalTrials.gov NCT00060372.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer*
  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacokinetics
  • Antigens, CD / immunology
  • Antigens, CD / metabolism*
  • Arthritis, Rheumatoid / chemically induced
  • CTLA-4 Antigen
  • Female
  • Graft vs Host Disease / etiology
  • Graft vs Leukemia Effect / drug effects*
  • Humans
  • Ipilimumab
  • Kaplan-Meier Estimate
  • Leukemia / mortality
  • Leukemia / therapy*
  • Lymphoma / mortality
  • Lymphoma / therapy
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / prevention & control*
  • Pneumonia / chemically induced
  • Transplantation, Homologous


  • Antibodies, Monoclonal
  • Antigens, CD
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Ipilimumab

Associated data

  • ClinicalTrials.gov/NCT00060372