Active idiotypic vaccination versus control immunotherapy for follicular lymphoma.

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.

• Authors: 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
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 32 Issue 17 Pg. 1797-803 (Jun 10 2014) ISSN: 1527-7755 [Electronic] United States
• PMID: 24799467 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 by American Society of Clinical Oncology.

Chemical References

• Cancer Vaccines
• Immunoglobulin Idiotypes
• Vincristine
• Granulocyte-Macrophage Colony-Stimulating Factor
• Cyclophosphamide
• Hemocyanins
• keyhole-limpet hemocyanin
• Prednisone

Topics

• Adult
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Cancer Vaccines (administration & dosage, adverse effects, immunology)
• Cyclophosphamide (administration & dosage)
• Double-Blind Method
• Female
• Granulocyte-Macrophage Colony-Stimulating Factor (administration & dosage, immunology)
• Hemocyanins (administration & dosage, immunology)
• Humans
• Immunoglobulin Idiotypes (immunology)
• Immunotherapy (methods)
• Lymphoma, Follicular (drug therapy, immunology, therapy)
• Male
• Middle Aged
• Prednisone (administration & dosage)
• Vincristine (administration & dosage)