Rituximab and intravenous immune globulin for desensitization during renal transplantation

N Engl J Med. 2008 Jul 17;359(3):242-51. doi: 10.1056/NEJMoa0707894.

Abstract

Background: Few options for transplantation currently exist for patients highly sensitized to HLA. This exploratory, open-label, phase 1-2, single-center study examined whether intravenous immune globulin plus rituximab could reduce anti-HLA antibody levels and improve transplantation rates.

Methods: Between September 2005 and May 2007, a total of 20 highly sensitized patients (with a mean [+/-SD] T-cell panel-reactive antibody level, determined by use of the complement-dependent cytotoxicity assay, of 77+/-19% or with donor-specific antibodies) were enrolled and received treatment with intravenous immune globulin and rituximab. We recorded rates of transplantation, panel-reactive antibody levels, cross-matching results at the time of transplantation, survival of patients and grafts, acute rejection episodes, serum creatinine values, adverse events and serious adverse events, and immunologic factors.

Results: The mean panel-reactive antibody level was 44+/-30% after the second infusion of intravenous immune globulin (P<0.001 for the comparison with the pretreatment level). At study entry, the mean time on dialysis among recipients of a transplant from a deceased donor was 144+/-89 months (range, 60 to 324). However, the time to transplantation after desensitization was 5+/-6 months (range, 2 to 18). Sixteen of the 20 patients (80%) received a transplant. At 12 months, the mean serum creatinine level was 1.5+/-1.1 mg per deciliter (133+/-97 micromol per liter), and the mean survival rates of patients and grafts were 100% and 94%, respectively. There were no infusion-related adverse events or serious adverse events during the study. Long-term monitoring for infectious complications and neurologic problems revealed no unanticipated events.

Conclusions: These findings suggest that the combination of intravenous immune globulin and rituximab may prove effective as a desensitization regimen for patients awaiting a transplant from either a living donor or a deceased donor. Larger and longer trials are needed to evaluate the clinical efficacy and safety of this approach. (ClinicalTrials.gov number, NCT00642655.)

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies / blood
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD19 / blood
  • Antigens, CD20 / immunology*
  • Creatinine / blood
  • Desensitization, Immunologic / methods
  • Drug Therapy, Combination
  • Female
  • Graft Rejection / epidemiology
  • HLA Antigens / immunology*
  • Humans
  • Immunoglobulins, Intravenous / adverse effects
  • Immunoglobulins, Intravenous / therapeutic use*
  • Immunologic Factors / adverse effects
  • Immunologic Factors / therapeutic use*
  • Immunosuppression / methods*
  • Kidney Transplantation / immunology*
  • Male
  • Middle Aged
  • Rituximab
  • Survival Rate

Substances

  • Antibodies
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD19
  • Antigens, CD20
  • HLA Antigens
  • Immunoglobulins, Intravenous
  • Immunologic Factors
  • Rituximab
  • Creatinine

Associated data

  • ClinicalTrials.gov/NCT00642655