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© The Author 2006. Published by Oxford University Press.
ARTICLE |
Clinical Benefit Associated With Idiotypic Vaccination in Patients With Follicular Lymphoma
Affiliations of authors: Lab of Immunotherapy, Oncology Division, Center for Applied Medical Research, University of Navarra, Pamplona, Spain (SI, MRC, NZ, ALD, HV, ES, MB); General Flow Cytometry Service, Center for Cancer Investigation, University of Salamanca, Salamanca, Spain (LS, ARC, AO); Department of Immunology (FP), Department of Hematology (RGM, CP, JPC, ER), Cell Therapy Area (IM), University Clinic, University of Navarra, Pamplona, Spain
Correspondence to: Maurizio Bendandi, MD, PhD, Lab of Immunotherapy, Oncology Division, Rm. 1.06, Center for Applied Medical Research (CIMA), Avda. Pio XII, 55, 31008 Pamplona (Navarra), Spain (e-mail: mbendandi{at}unav.es).
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.
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- Idiotype Vaccination in Follicular Lymphoma: Knocking on the Doorway to Cure
- Dan L. Longo
J Natl Cancer Inst 2006 98: 1263-1265.[Extract] [Full Text] [PDF]
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