title: 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.
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.
authors.affiliation: Department of Internal Medicine II: Hematology and Oncology, University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Zimmermann
authors.affiliation: Department of Hematology, Charite University Hospitals, Campus Virchow-Klinikum, 13353 Berlin, Germany.
authors.forename: Theresa
authors.initials: T
authors.lastname: Weiland
authors.affiliation: Clinical Immunohaematology Laboratory, Queensland Institute of Medical Research, Brisbane QLD 4006, Australia.
authors.forename: Jamie P
authors.initials: JP
authors.lastname: Nourse
authors.affiliation: Clinical Immunohaematology Laboratory, Queensland Institute of Medical Research, Brisbane QLD 4006, Australia.
authors.forename: Maher K
authors.initials: MK
authors.lastname: Gandhi
authors.affiliation: Department of Nephrology and Intensive Care, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, 13353 Berlin, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Reinke
authors.affiliation: Department of Abdominal and Transplant Surgery, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, 13353 Berlin, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Neuhaus
authors.affiliation: Department of Medical Genetics, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, 13353 Berlin, Germany.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Karbasiyan
authors.affiliation: Department of Microbiology, Saarland University Hospital, 66421 Homburg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Gärtner
authors.affiliation: Department of Pathology, Charité-Universitätsmedizin Berlin, Campus Mitte, 10117 Berlin, Germany.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Anagnostopoulos
authors.affiliation: Department of Hematology, Charite University Hospitals, Campus Virchow-Klinikum, 13353 Berlin, Germany.
authors.forename: Hanno
authors.initials: H
authors.lastname: Riess
authors.affiliation: Department of Internal Medicine II: Hematology and Oncology, University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany ; Department of Hematology, Charite University Hospitals, Campus Virchow-Klinikum, 13353 Berlin, Germany.
authors.forename: Ralf U
authors.initials: RU
authors.lastname: Trappe
authors.affiliation: Global Medical Affairs Oncology, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Oertel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016867:Immunocompromised Host; D008232:Lymphoproliferative Disorders / Q000188:drug therapy* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics*; D000069283:Rituximab; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; C496124:FCGR3A protein, human; D017452:Receptors, IgG; D000069283:Rituximab
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