Active idiotypic vaccination versus control immunotherapy for follicular lymphoma
Ronald Levy, Kristen N Ganjoo, John P Leonard, Julie M Vose, Ian W Flinn, Richard F Ambinder, Joseph M Connors, Neil L Berinstein, Andrew R Belch, Nancy L Bartlett, Craig Nichols, Christos E Emmanouilides, John M Timmerman, Stephanie A Gregory, Brian K Link, David J Inwards, Arnold S Freedman, Jeffrey V Matous, Michael J Robertson, Lori A Kunkel, Diane E Ingolia, Andrew J Gentles, Chih Long Liu, Robert Tibshirani, Ash A Alizadeh, Dan W Denney Jr, Ronald Levy, Kristen N Ganjoo, John P Leonard, Julie M Vose, Ian W Flinn, Richard F Ambinder, Joseph M Connors, Neil L Berinstein, Andrew R Belch, Nancy L Bartlett, Craig Nichols, Christos E Emmanouilides, John M Timmerman, Stephanie A Gregory, Brian K Link, David J Inwards, Arnold S Freedman, Jeffrey V Matous, Michael J Robertson, Lori A Kunkel, Diane E Ingolia, Andrew J Gentles, Chih Long Liu, Robert Tibshirani, Ash A Alizadeh, Dan W Denney Jr
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.
Trial registration: ClinicalTrials.gov NCT00017290.
Conflict of interest statement
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
© 2014 by American Society of Clinical Oncology.
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Source: PubMed