Active idiotypic vaccination versus control immunotherapy for follicular
lymphoma.
Author(s): Levy R(1), Ganjoo KN(1), Leonard JP(1), Vose JM(1), Flinn IW(1), Ambinder RF(1),
Connors JM(1), Berinstein NL(1), Belch AR(1), Bartlett NL(1), Nichols C(1),
Emmanouilides CE(1), Timmerman JM(1), Gregory SA(1), Link BK(1), Inwards DJ(1),
Freedman AS(1), Matous JV(1), Robertson MJ(1), Kunkel LA(1), Ingolia DE(1),
Gentles AJ(1), Liu CL(1), Tibshirani R(1), Alizadeh AA(2), Denney DW Jr(1).
Affiliation(s): 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.
Publication date & source: 2014, J Clin Oncol. , 32(17):1797-803
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.
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