Active Idiotypic Vaccination Versus Control Immunotherapy for Follicular Lymphoma

作者:Levy Ronald; Ganjoo Kristen N; Leonard John P; Vose Julie M; Flinn Ian W; Ambinder Richard F; Connors Joseph M; Berinstein Neil L; Belch Andrew R; Bartlett Nancy L; Nichols Craig; Emmanouilides Christos E; Timmerman John M; Gregory Stephanie A; Link Brian K; Inwards David J; Freedman Arnold S; Matous Jeffrey V; Robertson Michael J; Kunkel Lori A; Ingolia Diane E; Gentles Andrew J; Liu Chih Long; Tibshirani Robert; Alizadeh Ash A*; Denney Dan W Jr
来源:Journal of Clinical Oncology, 2014, 32(17): 1797-U75.
DOI:10.1200/JCO.2012.43.9273

摘要

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. %26lt;br%26gt;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. %26lt;br%26gt;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. %26lt;br%26gt;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.

  • 出版日期2014-6-10