Vaccination With Patient-Specific Tumor-Derived Antigen in First Remission Improves Disease-Free Survival in Follicular Lymphoma
Vaccination With Patient-Specific Tumor-Derived Antigen in First Remission Improves Disease-Free Survival in Follicular Lymphoma
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DOI：
10.1200/jco.2010.33.3005
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发表时间：
2011-07-10
影响因子：
45.3
通讯作者：
Kwak, Larry W.
中科院分区：
文献类型：
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作者：
Schuster, Stephen J.;Neelapu, Sattva S.;Kwak, Larry W.
目的用杂交瘤来源的自体肿瘤免疫球蛋白（IG）独特型（Id）偶联钥孔血蓝蛋白（KLH）并与粒细胞-单核细胞集落刺激因子（GM-CSF）联合免疫诱导滤泡性淋巴瘤（FL）特异性免疫应答。为了确定这种疫苗的临床效益，我们进行了一个双盲多中心对照III期trial.Patients和MethodsTreatment初治患者与晚期FL达到完全反应（CR）或CR未经证实（CRu）化疗后随机分配两个到一个接受Id疫苗（Id KLH + GM-CSF）或控制（KLH + GM-CSF）。主要疗效终点是无病生存期（DFS）为所有随机分配的患者和DFS随机分配的患者接受至少一个剂量的Id疫苗或control.ResultsOf 234例患者入组，177（81%）实现CR/CRu化疗后，并随机分配。对于177例随机分配的患者，包括60例因复发（n = 55）或其他原因（n = 5）而未接种疫苗的患者，Id疫苗组和对照组之间的中位DFS分别为23.0和20.6个月（风险比[HR]，0.81; 95%CI，0.56至1.16; P = 0.256）。对于接受Id疫苗（n = 76）或对照（n = 41）的117例患者，随机化后Id疫苗组的中位DFS为44.2个月，对照组为30.6个月（HR，0.62; 95% CI，0.39至0.99; P = 0.047），中位随访时间为56.6个月（范围，12.6至89.3个月）。在计划外亚组分析中，接受IgM-Id治疗的患者中位DFS显著延长，（52.9 vs 28.7个月; P = .001），但不是IgG-Id疫苗（35.1比32.4个月; P = .807）与同种型匹配的对照治疗患者相比。CRu可能延长FL患者的DFS。疫苗同种型可能影响临床结果，并解释本试验与其他对照Id疫苗试验之间的不同结果。
PurposeVaccination with hybridoma-derived autologous tumor immunoglobulin (Ig) idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) and administered with granulocyte-monocyte colony-stimulating factor (GM-CSF) induces follicular lymphoma (FL) -specific immune responses. To determine the clinical benefit of this vaccine, we conducted a double-blind multicenter controlled phase III trial.Patients and MethodsTreatment-naive patients with advanced stage FL achieving complete response (CR) or CR unconfirmed (CRu) after chemotherapy were randomly assigned two to one to receive either Id vaccine (Id-KLH + GM-CSF) or control (KLH + GM-CSF). Primary efficacy end points were disease-free survival (DFS) for all randomly assigned patients and DFS for randomly assigned patients receiving at least one dose of Id vaccine or control.ResultsOf 234 patients enrolled, 177 (81%) achieved CR/CRu after chemotherapy and were randomly assigned. For 177 randomly assigned patients, including 60 patients not vaccinated because of relapse (n = 55) or other reasons (n = 5), median DFS between Id-vaccine and control arms was 23.0 versus 20.6 months, respectively (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.16; P = .256). For 117 patients who received Id vaccine (n = 76) or control (n = 41), median DFS after randomization was 44.2 months for Id-vaccine arm versus 30.6 months for control arm (HR, 0.62; 95% CI, 0.39 to 0.99; P = .047) at median follow-up of 56.6 months (range, 12.6 to 89.3 months). In an unplanned subgroup analysis, median DFS was significantly prolonged for patients receiving IgM-Id (52.9 v 28.7 months; P = .001) but not IgG-Id vaccine (35.1 v 32.4 months; P = .807) compared with isotype-matched control-treated patients.ConclusionVaccination with patient-specific hybridoma-derived Id vaccine after chemotherapy-induced CR/CRu may prolong DFS in patients with FL. Vaccine isotype may affect clinical outcome and explain differing results between this and other controlled Id-vaccine trials.