title: Serious pulmonary toxicity in patients with Hodgkin's lymphoma with SGN-30, gemcitabine, vinorelbine, and liposomal doxorubicin is associated with an FcγRIIIa-158 V/F polymorphism.
abstract: BACKGROUND
  Based on in vitro synergistic cytotoxicity when anti-CD30 antibodies are combined with gemcitabine, the Cancer and Leukemia Group B conducted a double-blind, randomized, phase II trial of SGN-30 with gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD) in patients with relapsed Hodgkin's lymphoma.
  
  
  METHODS
  In part 1 of the trial, 16 patients received SGN-30 with GVD to assess the safety of the combination. In part 2, patients were randomly allocated to SGN-30 (n = 7) or placebo (n = 7) with GVD to determine overall response rate (ORR).
  
  
  RESULTS
  ORR in all 30 patients was 63% (65% with SGN-30 plus GVD, n = 23, and 57% with placebo plus GVD, n = 7). Median event-free survival was 9.0 months, with no difference between the two arms. Grades 3-5 pneumonitis occurred in five patients receiving SGN-30 and GVD, leading to premature closure of the trial. All five patients with pulmonary toxicity had a V/F polymorphism in the FcγRIIIa gene (P = 0.008).
  
  
  CONCLUSIONS
  Together with historical data demonstrating a 2% incidence of pulmonary events with GVD, these results indicate that SGN-30 cannot safely be administered concurrently. The risk of pneumonitis with SGN-30 and GVD is greatest in patients with an FcγRIIIa V/F polymorphism.
authors.affiliation: Division of Hematology-Oncology, The Ohio State University Medical Center, Columbus, OH. Electronic address: kristie.blum@osumc.edu.
authors.forename: K A
authors.initials: KA
authors.lastname: Blum
authors.affiliation: CALGB Statistical Center, Duke University Medical Center, Durham, NC.
authors.forename: S-H
authors.initials: SH
authors.lastname: Jung
authors.affiliation: CALGB Statistical Center, Duke University Medical Center, Durham, NC.
authors.forename: J L
authors.initials: JL
authors.lastname: Johnson
authors.affiliation: Division of Hematology-Oncology, The Ohio State University Medical Center, Columbus, OH.
authors.forename: T S
authors.initials: TS
authors.lastname: Lin
authors.affiliation: Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH.
authors.forename: E D
authors.initials: ED
authors.lastname: Hsi
authors.affiliation: Division of Hematology-Oncology, The Ohio State University Medical Center, Columbus, OH.
authors.forename: D M
authors.initials: DM
authors.lastname: Lucas
authors.affiliation: Division of Hematology-Oncology, The Ohio State University Medical Center, Columbus, OH.
authors.forename: J C
authors.initials: JC
authors.lastname: Byrd
authors.affiliation: Division of Hematology-Oncology, Georgetown University Hospital, Washington, DC.
authors.forename: B D
authors.initials: BD
authors.lastname: Cheson
authors.affiliation: Division of Hematology-Oncology, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: N L
authors.initials: NL
authors.lastname: Bartlett
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004311:Double-Blind Method; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008171:Lung Diseases / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011092:Polyethylene Glycols / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017452:Receptors, IgG / Q000235:genetics*; D015996:Survival Rate; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D055815:Young Adult; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; C496124:FCGR3A protein, human; D017452:Receptors, IgG; C506643:liposomal doxorubicin; D003841:Deoxycytidine; D011092:Polyethylene Glycols; D014747:Vinblastine; D004317:Doxorubicin; C504717:SGN-30 monoclonal antibody; D000077235:Vinorelbine; D000093542:Gemcitabine