title: Phase II trial of idiotype vaccination in previously treated patients with indolent non-Hodgkin's lymphoma resulting in durable clinical responses.
abstract: OBJECTIVE
  To evaluate idiotype (Id) vaccination as a single agent in previously treated patients with indolent non-Hodgkin's lymphoma.
  
  
  METHODS
  Patients underwent biopsy for determination of their lymphoma-specific Id sequence. Recombinant Id protein was manufactured and covalently linked with keyhole limpet hemocyanin (KLH) to generate Id/KLH. Patients received Id/KLH 1 mg on day 1 subcutaneously, with granulocyte-macrophage colony-stimulating factor 250 mug on days 1 to 4, monthly for 6 months. Booster injections were administered until progression. Both clinical and immune responses were evaluated.
  
  
  RESULTS
  Thirty-two previously treated patients received at least one injection of Id/KLH, and 31 were assessed for efficacy. Responses were observed in four patients (one complete response and three partial responses). Median time to onset of response was 5.9 months (range, 2.3 to 14.1 months). Median duration of response has not been reached but should be at least 19.4 months (range, 10.4 to 27.2+ months). Median time to progression is 13.5 months. The most common adverse events were mild to moderate injection site reactions. Six (67%) of nine patients tested demonstrated a cellular immune response, and four (20%) of 20 patients demonstrated an antibody response against their Id.
  
  
  CONCLUSIONS
  This trial demonstrates that Id/KLH alone can induce tumor regression and durable objective responses. Further study of Id/KLH is recommended in other settings where efficacy may be further enhanced as in first-line therapy or after cytoreductive therapy.
authors.affiliation: Sharp Healthcare, San Diego, CA, USA.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Redfern
authors.forename: Troy H
authors.initials: TH
authors.lastname: Guthrie
authors.forename: Alberto
authors.initials: A
authors.lastname: Bessudo
authors.forename: John J
authors.initials: JJ
authors.lastname: Densmore
authors.forename: Peter R
authors.initials: PR
authors.lastname: Holman
authors.forename: Nalini
authors.initials: N
authors.lastname: Janakiraman
authors.forename: John P
authors.initials: JP
authors.lastname: Leonard
authors.forename: Richard L
authors.initials: RL
authors.lastname: Levy
authors.forename: Richard G
authors.initials: RG
authors.lastname: Just
authors.forename: Mitchell R
authors.initials: MR
authors.lastname: Smith
authors.forename: Fred P
authors.initials: FP
authors.lastname: Rosenfelt
authors.forename: Peter H
authors.initials: PH
authors.lastname: Wiernik
authors.forename: William D
authors.initials: WD
authors.lastname: Carter
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Gold
authors.forename: Teresa J
authors.initials: TJ
authors.lastname: Melink
authors.forename: John C
authors.initials: JC
authors.lastname: Gutheil
authors.forename: John F
authors.initials: JF
authors.lastname: Bender
mesh_terms: D000328:Adult; D000368:Aged; D000917:Antibody Formation; D019496:Cancer Vaccines; D005260:Female; D006433:Hemocyanins; D006801:Humans; D007111:Immunity, Cellular; D007130:Immunoglobulin Idiotypes / Q000627:therapeutic use*; D007167:Immunotherapy / Q000379:methods*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; D007130:Immunoglobulin Idiotypes; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin