Journal Article

Clinical Benefit Associated With Idiotypic Vaccination in Patients With Follicular Lymphoma

Susana Inogès, Mercedes Rodrìguez-Calvillo, Natalia Zabalegui, Ascensiòn Lòpez-Dìaz de Cerio, Helena Villanueva, Elena Soria, Lilia Suárez, Arancha Rodríguez-Caballero, Fernando Pastor, Ricardo García-Muñóz, Carlos Panizo, Javier Pèrez-Calvo, Ignacio Melero, Eduardo Rocha, Alberto Orfao and Maurizio Bendandi

in JNCI: Journal of the National Cancer Institute

Volume 98, issue 18, pages 1292-1301
Published in print September 2006 | ISSN: 0027-8874
Published online September 2006 | e-ISSN: 1460-2105 | DOI: https://dx.doi.org/10.1093/jnci/djj358
Clinical Benefit Associated With Idiotypic Vaccination in Patients With Follicular Lymphoma

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Background: 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. Methods: 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. Results: 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). Conclusions: 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.

Journal Article.  7082 words.  Illustrated.

Subjects: Medical Oncology

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