Clinical benefit associated with idiotypic vaccination in patients with follicular lymphoma.
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.
Inogès
Susana
S
Lab of Immunotherapy, Oncology Division, Center for Applied Medical Research (CIMA), Avda. Pio XII, 55, 31008 Pamplona (Navarra), Spain.
Rodrìguez-Calvillo
Mercedes
M
Zabalegui
Natalia
N
Lòpez-Dìaz de Cerio
Ascensiòn
A
Villanueva
Helena
H
Soria
Elena
E
Suárez
Lilia
L
Rodríguez-Caballero
Arancha
A
Pastor
Fernando
F
García-Muñóz
Ricardo
R
Panizo
Carlos
C
Pèrez-Calvo
Javier
J
Melero
Ignacio
I
Rocha
Eduardo
E
Orfao
Alberto
A
Bendandi
Maurizio
M
D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology / Q000627:therapeutic use*; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011961:Receptors, Fc / Q000235:genetics; D016019:Survival Analysis; D016896:Treatment Outcome
D019496:Cancer Vaccines; D007130:Immunoglobulin Idiotypes; D019253:Proto-Oncogene Proteins c-bcl-2; D011961:Receptors, Fc