J Clin Oncol. 2014 Jun 10;32(17):1797-803. doi: 10.1200/JCO.2012.43.9273. Epub 2014 May 5.

Active idiotypic vaccination versus control immunotherapy for follicular lymphoma.

Levy R¹, Ganjoo KN¹, Leonard JP¹, Vose JM¹, Flinn IW¹, Ambinder RF¹, Connors JM¹, Berinstein NL¹, Belch AR¹, Bartlett NL¹, Nichols C¹, Emmanouilides CE¹, Timmerman JM¹, Gregory SA¹, Link BK¹, Inwards DJ¹, Freedman AS¹, Matous JV¹, Robertson MJ¹, Kunkel LA¹, Ingolia DE¹, Gentles AJ¹, Liu CL¹, Tibshirani R¹, Alizadeh AA², Denney DW Jr¹.

Author information

1: Ronald Levy, Andrew J. Gentles, Chih Long Liu, Robert Tibshirani, and Ash A. Alizadeh, Stanford University Medical Center, Palo Alto; Christos E. Emmanouilides and John M. Timmerman, University of California Los Angeles Medical Center, Los Angeles; Lori A. Kunkel, Diane E. Ingolia, and Dan W. Denney Jr, Genitope, Fremont, CA; Kristen N. Ganjoo and Michael J. Robertson, Indiana University Medical Center, Indianapolis, IN; John P. Leonard, Weill Medical College of Cornell University, New York, NY; Julie M. Vose, University of Nebraska Medical Center, Omaha, NE; Ian W. Flinn and Richard F. Ambinder, Johns Hopkins University Oncology Center, Baltimore, MD; Joseph M. Connors, British Columbia Cancer Agency Centre for Lymphoid Cancer, Vancouver, British Columbia; Neil L. Berinstein, Toronto-Sunnybrook Regional Cancer Centre, Toronto, Ontario; Andrew R. Belch, Cross Cancer Institute, Edmonton, Alberta, Canada; Nancy L. Bartlett, Washington University School of Medicine, St Louis, MO; Craig Nichols, Oregon Health Science University, Portland, OR; Stephanie A. Gregory, Rush University Medical Center, Chicago, IL; Brian K. Link, University of Iowa Hospitals and Clinics, Iowa City, IA; David J. Inwards, Mayo Clinic, Rochester, MN; Arnold S. Freedman, Dana-Farber Cancer Institute, Boston, MA; and Jeffrey V. Matous, Rocky Mountain Cancer Centers, Denver, CO.
2: Ronald Levy, Andrew J. Gentles, Chih Long Liu, Robert Tibshirani, and Ash A. Alizadeh, Stanford University Medical Center, Palo Alto; Christos E. Emmanouilides and John M. Timmerman, University of California Los Angeles Medical Center, Los Angeles; Lori A. Kunkel, Diane E. Ingolia, and Dan W. Denney Jr, Genitope, Fremont, CA; Kristen N. Ganjoo and Michael J. Robertson, Indiana University Medical Center, Indianapolis, IN; John P. Leonard, Weill Medical College of Cornell University, New York, NY; Julie M. Vose, University of Nebraska Medical Center, Omaha, NE; Ian W. Flinn and Richard F. Ambinder, Johns Hopkins University Oncology Center, Baltimore, MD; Joseph M. Connors, British Columbia Cancer Agency Centre for Lymphoid Cancer, Vancouver, British Columbia; Neil L. Berinstein, Toronto-Sunnybrook Regional Cancer Centre, Toronto, Ontario; Andrew R. Belch, Cross Cancer Institute, Edmonton, Alberta, Canada; Nancy L. Bartlett, Washington University School of Medicine, St Louis, MO; Craig Nichols, Oregon Health Science University, Portland, OR; Stephanie A. Gregory, Rush University Medical Center, Chicago, IL; Brian K. Link, University of Iowa Hospitals and Clinics, Iowa City, IA; David J. Inwards, Mayo Clinic, Rochester, MN; Arnold S. Freedman, Dana-Farber Cancer Institute, Boston, MA; and Jeffrey V. Matous, Rocky Mountain Cancer Centers, Denver, CO. arasha@stanford.edu.

Abstract

PURPOSE:

Idiotypes (Ids), the unique portions of tumor immunoglobulins, can serve as targets for passive and active immunotherapies for lymphoma. We performed a multicenter, randomized trial comparing a specific vaccine (MyVax), comprising Id chemically coupled to keyhole limpet hemocyanin (KLH) plus granulocyte macrophage colony-stimulating factor (GM-CSF) to a control immunotherapy with KLH plus GM-CSF.

PATIENTS AND METHODS:

Patients with previously untreated advanced-stage follicular lymphoma (FL) received eight cycles of chemotherapy with cyclophosphamide, vincristine, and prednisone. Those achieving sustained partial or complete remission (n=287 [44%]) were randomly assigned at a ratio of 2:1 to receive one injection per month for 7 months of MyVax or control immunotherapy. Anti-Id antibody responses (humoral immune responses [IRs]) were measured before each immunization. The primary end point was progression-free survival (PFS). Secondary end points included IR and time to subsequent antilymphoma therapy.

RESULTS:

At a median follow-up of 58 months, no significant difference was observed in either PFS or time to next therapy between the two arms. In the MyVax group (n=195), anti-Id IRs were observed in 41% of patients, with a median PFS of 40 months, significantly exceeding the median PFS observed in patients without such Id-induced IRs and in those receiving control immunotherapy.

CONCLUSION:

This trial failed to demonstrate clinical benefit of specific immunotherapy. The subset of vaccinated patients mounting specific anti-Id responses had superior outcomes. Whether this reflects a therapeutic benefit or is a marker for more favorable underlying prognosis requires further study.