title: Vaccination with patient-specific tumor-derived antigen in first remission improves disease-free survival in follicular lymphoma.
abstract: OBJECTIVE
  Vaccination with hybridoma-derived autologous tumor immunoglobulin (Ig) idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) and administered with granulocyte-monocyte colony-stimulating factor (GM-CSF) induces follicular lymphoma (FL) -specific immune responses. To determine the clinical benefit of this vaccine, we conducted a double-blind multicenter controlled phase III trial.
  
  
  METHODS
  Treatment-naive patients with advanced stage FL achieving complete response (CR) or CR unconfirmed (CRu) after chemotherapy were randomly assigned two to one to receive either Id vaccine (Id-KLH + GM-CSF) or control (KLH + GM-CSF). Primary efficacy end points were disease-free survival (DFS) for all randomly assigned patients and DFS for randomly assigned patients receiving at least one dose of Id vaccine or control.
  
  
  RESULTS
  Of 234 patients enrolled, 177 (81%) achieved CR/CRu after chemotherapy and were randomly assigned. For 177 randomly assigned patients, including 60 patients not vaccinated because of relapse (n = 55) or other reasons (n = 5), median DFS between Id-vaccine and control arms was 23.0 versus 20.6 months, respectively (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.16; P = .256). For 117 patients who received Id vaccine (n = 76) or control (n = 41), median DFS after randomization was 44.2 months for Id-vaccine arm versus 30.6 months for control arm (HR, 0.62; 95% CI, 0.39 to 0.99; P = .047) at median follow-up of 56.6 months (range, 12.6 to 89.3 months). In an unplanned subgroup analysis, median DFS was significantly prolonged for patients receiving IgM-Id (52.9 v 28.7 months; P = .001) but not IgG-Id vaccine (35.1 v 32.4 months; P = .807) compared with isotype-matched control-treated patients.
  
  
  CONCLUSIONS
  Vaccination with patient-specific hybridoma-derived Id vaccine after chemotherapy-induced CR/CRu may prolong DFS in patients with FL. Vaccine isotype may affect clinical outcome and explain differing results between this and other controlled Id-vaccine trials.
authors.affiliation: Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Schuster
authors.forename: Sattva S
authors.initials: SS
authors.lastname: Neelapu
authors.forename: Barry L
authors.initials: BL
authors.lastname: Gause
authors.forename: John E
authors.initials: JE
authors.lastname: Janik
authors.forename: Franco M
authors.initials: FM
authors.lastname: Muggia
authors.forename: Jon P
authors.initials: JP
authors.lastname: Gockerman
authors.forename: Jane N
authors.initials: JN
authors.lastname: Winter
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Flowers
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Nikcevich
authors.forename: Eduardo M
authors.initials: EM
authors.lastname: Sotomayor
authors.forename: Dean S
authors.initials: DS
authors.lastname: McGaughey
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: Elise A
authors.initials: EA
authors.lastname: Chong
authors.forename: Craig W
authors.initials: CW
authors.lastname: Reynolds
authors.forename: Donald A
authors.initials: DA
authors.lastname: Berry
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Santos
authors.forename: Mihaela A
authors.initials: MA
authors.lastname: Popa
authors.forename: Amy M
authors.initials: AM
authors.lastname: McCord
authors.forename: Larry W
authors.initials: LW
authors.lastname: Kwak
mesh_terms: D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D008224:Lymphoma, Follicular / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D057285:Precision Medicine; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; D007130:Immunoglobulin Idiotypes