Clinical outcome of lymphoma patients after idiotype vaccination is correlated with humoral immune response and immunoglobulin G Fc receptor genotype.
OBJECTIVE
The unique immunoglobulin idiotype (Id) expressed by each B-cell lymphoma is a target for immunotherapy. Vaccination with Id induces humoral and/or cellular anti-Id immune responses. However, the clinical impact of these anti-Id immune responses is unknown. We and others have previously reported that immunoglobulin G Fc receptor (FcgammaR) polymorphisms predict the clinical response of lymphoma patients to passive anti-CD20 antibody infusions. In this study, we tested whether anti-Id immune responses or FcgammaR polymorphisms associate with clinical outcome of patients who received Id vaccination.


METHODS
We analyzed 136 patients with follicular lymphoma who had received Id vaccination. The anti-Id immune responses were measured and FcgammaRIIIa and FcgammaRIIa polymorphisms were determined and correlated with clinical outcome for these patients.


RESULTS
Patients who mounted humoral immune responses had a longer progression-free survival (PFS) than those who did not (8.21 v 3.38 years; P = .018). Patients with FcgammaRIIIa 158 valine/valine (V/V) genotype also had a longer PFS than those with valine/phenylalanine (V/F) or phenylalanine/phenylalanine (F/F) genotypes (V/V, 8.21 v V/F, 3.38 years; P = .004; v F/F, 4.47 years; P = .035). Multivariate analysis using the Cox proportional hazards model showed that V/V genotype and humoral immune responses were independent positive predictors for PFS.


CONCLUSIONS
This study is the first to identify the predictive value of FcgammaR polymorphism on clinical outcome in patients who received active immunotherapy with tumor antigen vaccines. Our results imply that the antibodies induced against a tumor antigen are beneficial and that FcgammaR-bearing cells mediate an antitumor effect by killing antibody-coated tumor cells.
Division of Oncology, Department of Internal Medicine, Stanford University School of Medicine, Stanford, CA 94305-5306, USA.
Wen-Kai
WK
Weng
Debra
D
Czerwinski
John
J
Timmerman
Frank J
FJ
Hsu
Ronald
R
Levy
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000627:therapeutic use*; D016233:Immunotherapy, Active / Q000379:methods; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000628:therapy; D008224:Lymphoma, Follicular / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008297:Male; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods
D015703:Antigens, CD; C080568:Fc gamma receptor IIA; D005819:Genetic Markers; D007130:Immunoglobulin Idiotypes; D017452:Receptors, IgG