Clinical benefit associated with idiotypic vaccination in patients with follicular lymphoma
Inogés S., Rodríguez-Calvillo M., Zabalegui N., López-Díaz de Cerio A., Villanueva H., Soria E., Suárez L., Rodríguez-Caballero A., Pastor F., García-Muñóz R., Panizo C., Pérez-Calvo J., Melero I., Rocha E., Orfao A., Bendandi M.
Grupo Español de Linfomas/Trasplante Autologo de Medula Oseo study group, Programa para el Estudio y Tratamiento de Hemopatias Malignas study group.
Lab of Immunotherapy, Oncology Division, Center for Applied Medical Research (CIMA), Avda. Pío XII, 55, 31008 Pamplona (Navarra), Spain.
Follicular 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.
Thirty-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.
Idiotype 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 (P<.0001) longer than both their first complete response (18 of 18 patients) and than the median duration of a CHOP-induced second complete response, i.e., 13 months (20 of 20 patients). The five nonresponders all had a second complete response that was shorter (median = 10 months; range = 8-13 months) than their first complete response (median = 17 months; range = 10-39 months).
Idiotypic 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.
CITATION J Natl Cancer Inst. 2006 Sep 20;98(18):1292-301