Fcγ-receptor IIIA polymorphism p.158F has no negative predictive impact on rituximab therapy with and without sequential chemotherapy in CD20-positive posttransplant lymphoproliferative disorder

J Immunol Res. 2014:2014:264723. doi: 10.1155/2014/264723. Epub 2014 Feb 10.

Abstract

We retrospectively analyzed the p.V158F polymorphism of Fcγ-receptor IIIA (FCGR3A, CD16) in patients with PTLD treated with rituximab monotherapy. Previous reports had indicated that the lower affinity F allele affects rituximab-mediated antibody-dependent cellular cytotoxicity (ADCC) and is linked to inferior outcome of rituximab monotherapy in B cell malignancies. 25 patients with PTLD after solid organ transplantation were included in this analysis. They had received 4 weekly doses of rituximab as part of two clinical trials, which had a rituximab monotherapy induction regimen in common. 16/25 patients received further treatment with CHOP-21 after rituximab monotherapy (PTLD-1, NCT01458548). The FCGR3A status was correlated to the response after 4 cycles of rituximab monotherapy. Response to rituximab monotherapy was not affected by F carrier status. This is in contrast to previous findings in B cell malignancies where investigators found a predictive impact of FCGR3A status on outcome to rituximab monotherapy. One explanation for this finding could be that ADCC is impaired in transplant recipients receiving immunosuppression. These results suggest that carrying a FCRG3A F allele does not negatively affect rituximab therapy in immunosuppressed patients.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Immunocompromised Host
  • Lymphoproliferative Disorders / drug therapy*
  • Lymphoproliferative Disorders / etiology*
  • Male
  • Middle Aged
  • Organ Transplantation / adverse effects
  • Polymorphism, Genetic*
  • Receptors, IgG / genetics*
  • Rituximab
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Agents
  • FCGR3A protein, human
  • Receptors, IgG
  • Rituximab