Originally published as JCO Early Release 10.1200/JCO.2004.06.003 on October 13 2004

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Clinical Outcome of Lymphoma Patients After Idiotype Vaccination Is Correlated With Humoral Immune Response and Immunoglobulin G Fc Receptor Genotype

From the Division of Medical Oncology, Department of Internal Medicine, Stanford University School of Medicine, Stanford, CA

Address reprint requests to Ronald Levy, MD, Division of Oncology CCSR 1126, 269 Campus Drive, Stanford University School of Medicine, Stanford, CA 94305-5306; e-mail: levy{at}stanford.edu

PURPOSE: 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 (FcR) 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 FcR polymorphisms associate with clinical outcome of patients who received Id vaccination.

PATIENTS AND METHODS: We analyzed 136 patients with follicular lymphoma who had received Id vaccination. The anti-Id immune responses were measured and FcRIIIa and FcRIIa 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 FcRIIIa 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.

CONCLUSION: This study is the first to identify the predictive value of FcR 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 FcR-bearing cells mediate an antitumor effect by killing antibody-coated tumor cells.

Supported by grant Nos. CA34233 and CA 33399 from the United States Public Health Service, National Institutes of Health. W.K.W. is recipient of a fellowship from Lymphoma Research Foundation. R.L. is an American Cancer Society Clinical Research Professor. J.T. is the recipient of a Clinical Associate Physician award from the National Institutes of Health (grant No. RR-00070-CAP).

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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