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BackgroundFollicular lymphoma is considered incurable, although cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy can induce sequential remissions. A patient's second complete response is typically shorter than that patient's first complete response. Idiotype vaccines can elicit specific immune responses and molecular remissions in patients with follicular lymphoma. However, a clinical benefit has never been formally proven.MethodsThirty-three consecutive follicular lymphoma patients in first relapse received six monthly cycles of CHOP-like chemotherapy. Patients who achieved a second complete response were vaccinated periodically for more than 2 years with autologous lymphoma-derived idiotype protein vaccine. Specific humoral and cellular responses were assessed, and patients were followed for disease recurrence. Statistical tests were two-sided.ResultsIdiotype vaccine could be produced for 25 patients who had a second complete response. In 20 patients (80%), a humoral (13/20) and/or a cellular (18/20) idiotype-specific response was detected. The median duration of the second complete response has not been reached, but it exceeds 33 months (range = 20+ to 51+ months). None of the 20 responders relapsed while undergoing active vaccination. All responders with enough follow-up for the comparison to be made experienced a second complete response that was statistically significantly (PConclusionsIdiotypic vaccination induced a specific immune response in the majority of patients with follicular lymphoma. Specific immune response was associated with a dramatic and highly statistically significant increase in disease-free survival. This is the first formal demonstration of clinical benefit associated with the use of a human cancer vaccine.

Original publication




Journal article


Journal of the National Cancer Institute

Publication Date





1292 - 1301


Lab of Immunotherapy, Oncology Division, Center for Applied Medical Research (CIMA), Avda. Pio XII, 55, 31008 Pamplona (Navarra), Spain.


Grupo Español de Linfomas/Trasplante Autologo de Medula Oseo study group, Programa para el Estudio y Tratamiento de Hemopatias Malignas study group, Humans, Lymphoma, Follicular, Neoplasm, Residual, Receptors, Fc, Proto-Oncogene Proteins c-bcl-2, Cancer Vaccines, Immunoglobulin Idiotypes, Neoplasm Staging, Disease-Free Survival, Treatment Outcome, Matched-Pair Analysis, Survival Analysis, Polymerase Chain Reaction, Polymorphism, Genetic, Adult, Aged, Middle Aged, Female, Male