Phase 2 trial of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia
Phase 2 trial of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia
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DOI：
10.1182/bloodadvances.2017014175
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发表时间：
2018-02-13
期刊：
影响因子：
7.5
通讯作者：
Scheinberg, David A.
中科院分区：
文献类型：
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作者：
Maslak, Peter G.;Dao, Tao;Scheinberg, David A.
美国国家癌症研究所（National Cancer Institute）一项关于癌症抗原优先排序的共识研究将Wilms tumor 1 （WT1）蛋白列为癌症免疫治疗的首要靶点。我们之前报道了一项针对急性髓性白血病（AML）患者的多价WT1肽疫苗（galinpepimut-S）的初步研究。我们现在已经进行了一项2期研究，研究这种疫苗在首次完全缓解（CR1）的成人AML患者中的应用。患者在10周内接受了6次疫苗接种，如果他们仍然处于CR1状态，则有可能每月接受6次额外的疫苗接种。接种第6次和第12次疫苗后，通过CD4(+) t细胞增殖、CD8(+) t细胞干扰素-g分泌（酶联免疫斑点）或CD8相关WT1肽主要组织相容性复合物四聚体测定（HLA-A*02患者）评估免疫应答（IRs）。22例患者（7例男性，中位年龄64岁）接受治疗。14例患者（64%）完成了>= 6次疫苗接种，9例（41%）接种了全部12剂疫苗。15例（68%）复发，10例（46%）死亡。该疫苗耐受性良好，最常见的毒性是1/2级注射部位反应（46%）、疲劳（32%）和皮肤硬化（32%）。CR1的中位无病生存期为16.9个月，而诊断后的总生存期尚未达到，但估计为>= 67.6个月。14名接受检测的患者中有9名（64%）在>= 1检测（CD4或CD8）中有IR。这些结果表明，WT1疫苗耐受性良好，刺激特异性IR，并与该队列患者的5年以上生存率相关。
A National Cancer Institute consensus study on prioritization of cancer antigens ranked the Wilms tumor 1 (WT1) protein as the top immunotherapy target in cancer. We previously reported a pilot study of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia (AML) patients. We have now conducted a phase 2 study investigating this vaccine in adults with AML in first complete remission (CR1). Patients received 6 vaccinations administered over 10 weeks with the potential to receive 6 additional monthly doses if they remained in CR1. Immune responses (IRs) were evaluated after the 6th and 12th vaccinations by CD4(+) T-cell proliferation, CD8(+) T-cell interferon-g secretion (enzyme-linked immunospot), or the CD8-relevant WT1 peptide major histocompatibility complex tetramer assay (HLA-A*02 patients only). Twenty-two patients (7 males; median age, 64 years) were treated. Fourteen patients (64%) completed >= 6 vaccinations, and 9 (41%) received all 12 vaccine doses. Fifteen patients (68%) relapsed, and 10 (46%) died. The vaccine was well tolerated, with the most common toxicities being grade 1/2 injection site reactions (46%), fatigue (32%), and skin induration (32%). Median disease-free survival from CR1 was 16.9 months, whereas the overall survival from diagnosis has not yet been reached but is estimated to be >= 67.6 months. Nine of 14 tested patients (64%) had an IR in >= 1 assay (CD4 or CD8). These results indicated that the WT1 vaccine was well tolerated, stimulated a specific IR, and was associated with survival in excess of 5 years in this cohort of patients.