Inogès Susana, Rodrìguez-Calvillo Mercedes, Zabalegui Natalia, Lòpez-Dìaz de Cerio Ascensiòn, Villanueva Helena, Soria Elena, Suárez Lilia, Rodríguez-Caballero Arancha, Pastor Fernando, García-Muñóz Ricardo, Panizo Carlos, Pèrez-Calvo Javier, Melero Ignacio, Rocha Eduardo, Orfao Alberto, Bendandi Maurizio
Lab of Immunotherapy, Oncology Division, Center for Applied Medical Research (CIMA), Avda. Pio XII, 55, 31008 Pamplona (Navarra), Spain.
J Natl Cancer Inst. 2006 Sep 20;98(18):1292-301. doi: 10.1093/jnci/djj358.
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.
尽管环磷酰胺、阿霉素、长春新碱和泼尼松（CHOP）化疗可诱导滤泡性淋巴瘤患者序贯缓解，但该疾病仍被认为无法治愈。患者的第二次完全缓解期通常短于第一次完全缓解期。独特型疫苗可引发滤泡性淋巴瘤患者的特异性免疫反应和分子缓解。然而，其临床益处从未得到正式证实。
33例首次复发的连续性滤泡性淋巴瘤患者接受了6个周期的类似CHOP方案的化疗。达到第二次完全缓解的患者接受自体淋巴瘤来源的独特型蛋白疫苗定期接种，为期2年以上。评估特异性体液和细胞反应，并对患者进行疾病复发随访。统计检验采用双侧检验。
25例达到第二次完全缓解的患者可制备独特型疫苗。20例患者（80%）检测到体液（13/20）和/或细胞（18/20）独特型特异性反应。第二次完全缓解期的中位数尚未达到，但超过33个月（范围为20+至51+个月）。20例有反应的患者在积极接种疫苗期间均未复发。所有有足够随访时间可进行比较的有反应患者，其第二次完全缓解期在统计学上显著长于其第一次完全缓解期（18例患者中的18例）以及CHOP诱导的第二次完全缓解期的中位数，即13个月（20例患者中的20例）（P<0.0001）。5例无反应患者的第二次完全缓解期均短于其第一次完全缓解期（中位数 = 10个月；范围 = 8 - 13个月），第一次完全缓解期的中位数为17个月（范围 = 10 - 39个月）。
独特型疫苗接种在大多数滤泡性淋巴瘤患者中诱导了特异性免疫反应。特异性免疫反应与无病生存期的显著且具有高度统计学意义的增加相关。这是使用人类癌症疫苗产生临床益处的首次正式证明。
