Department of Hematology/Oncology, University Medical Center Freiburg, Freiburg, Germany;
Blood. 2011 Feb 3;117(5):1483-91. doi: 10.1182/blood-2010-06-292342. Epub 2010 Nov 2.
Idiotype vaccination for follicular lymphoma is primarily being developed as remission consolidation after chemotherapy. We investigated idiotype vaccination as primary intervention for treatment-naive indolent B-cell lymphoma and in a separate cohort as remission consolidation after chemotherapy to assess immunization-induced immune responses in relation to progression-free survival (German Clinical Trials Register, DRKS00000227). Twenty-one patients in each cohort received 6 intradermal injections of adjuvanted recombinant idiotype Fab fragment (Fab(Id)); 76% of patients in both groups developed anti-idiotype antibodies and/or cellular immunity as measured by enzyme-linked immunosorbent assay and interferon-γ ELISpot. In treatment-naive patients, only cellular responses correlated with superior progression-free survival (P < .002) and durable objective remissions (P = .04). Immunization-induced T cells recognized hypermutated or complementarity-determining region 3 epitopes. After remission consolidation immunization, induction of anti-idiotype antibodies correlated with progression-free survival. Low B-cell counts after rituximab therapy predicted for failure to develop anti-idiotype antibodies. These results are similar to published trials showing an association of humoral immunity with control of residual lymphoma. In contrast, effective immunity against untreated lymphoma appears to be dependent on idiotype-specific T cells. Sustained remissions in patients with vaccination-induced cellular immunity suggest clinical benefit and warrant a randomized comparison of this vaccine with expectant management for asymptomatic follicular lymphoma.
针对滤泡性淋巴瘤的独特型疫苗接种主要是作为化疗后的缓解巩固治疗。我们研究了独特型疫苗接种作为治疗初治惰性 B 细胞淋巴瘤的一线干预措施，并在另一队列中作为化疗后的缓解巩固治疗，以评估与无进展生存期（德国临床试验注册中心，DRKS00000227）相关的免疫接种诱导的免疫反应。每个队列的 21 名患者接受了 6 次重组独特型 Fab 片段（Fab(Id))的皮内注射；两组中有 76%的患者产生了抗独特型抗体和/或细胞免疫，这是通过酶联免疫吸附试验和干扰素-γ ELISpot 来衡量的。在初治患者中，只有细胞反应与无进展生存期（P<0.002）和持久的客观缓解（P=0.04）相关。免疫诱导的 T 细胞识别了超突变或互补决定区 3 表位。在缓解巩固免疫接种后，抗独特型抗体的诱导与无进展生存期相关。利妥昔单抗治疗后 B 细胞计数低预测无法产生抗独特型抗体。这些结果与发表的试验相似，表明体液免疫与残留淋巴瘤的控制有关。相比之下，针对未经治疗的淋巴瘤的有效免疫似乎依赖于独特型特异性 T 细胞。接种诱导的细胞免疫患者的持续缓解提示临床获益，因此需要对这种疫苗与无症状滤泡性淋巴瘤的预期管理进行随机比较。
