儿童肿瘤学组 AALL0434：一项测试新诊断 T 细胞急性淋巴细胞白血病中奈拉滨的 III 期随机临床试验。
Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia.
机构信息
Virginia Tech Carilion School of Medicine and Carilion Clinic, Roanoke, VA.
Children's Minnesota Cancer and Blood Disorders Program, Minneapolis, MN.
出版信息
J Clin Oncol. 2020 Oct 1;38(28):3282-3293. doi: 10.1200/JCO.20.00256. Epub 2020 Aug 19.
PURPOSE
Nelarabine is effective in inducing remission in patients with relapsed and refractory T-cell acute lymphoblastic leukemia (T-ALL) but has not been fully evaluated in those with newly diagnosed disease.
PATIENTS AND METHODS
From 2007 to 2014, Children's Oncology Group trial AALL0434 (ClinicalTrials.gov identifier: NCT00408005) enrolled 1,562 evaluable patients with T-ALL age 1-31 years who received the augmented Berlin-Frankfurt-Muenster (ABFM) regimen with a 2 × 2 pseudo-factorial randomization to receive escalating-dose methotrexate (MTX) without leucovorin rescue plus pegaspargase (C-MTX) or high-dose MTX (HDMTX) with leucovorin rescue. Intermediate- and high-risk patients were also randomly assigned after induction to receive or not receive six 5-day courses of nelarabine that was incorporated into ABFM. Patients who experienced induction failure were nonrandomly assigned to HDMTX plus nelarabine. Patients with overt CNS disease (CNS3; ≥ 5 WBCs/μL with blasts) received HDMTX and were randomly assigned to receive or not receive nelarabine. All patients, except those with low-risk disease, received cranial irradiation.
RESULTS
The 5-year event-free and overall survival rates were 83.7% ± 1.1% and 89.5% ± 0.9%, respectively. The 5-year disease-free survival (DFS) rates for patients with T-ALL randomly assigned to nelarabine (n = 323) and no nelarabine (n = 336) were 88.2% ± 2.4% and 82.1% ± 2.7%, respectively ( = .029). Differences between DFS in a four-arm comparison were significant ( = .01), with no interactions between the MTX and nelarabine randomizations ( = .41). Patients treated with the best-performing arm, C-MTX plus nelarabine, had a 5-year DFS of 91% (n = 147). Patients who received nelarabine had significantly fewer isolated and combined CNS relapses compared with patients who did not receive nelarabine (1.3% ± 0.63% 6.9% ± 1.4%, respectively; = .0001). Toxicities, including neurotoxicity, were acceptable and similar between all four arms.
CONCLUSION
The addition of nelarabine to ABFM therapy improved DFS for children and young adults with newly diagnosed T-ALL without increased toxicity.
目的
奈拉滨可有效诱导复发/难治性 T 细胞急性淋巴细胞白血病（T-ALL）患者缓解，但尚未在新诊断疾病患者中进行充分评估。
方法
2007 年至 2014 年，儿童肿瘤学组试验 AALL0434（ClinicalTrials.gov 标识符：NCT00408005）纳入了 1562 例可评估的 1-31 岁 T-ALL 患者，他们接受了改良柏林-法兰克福-明斯特（ABFM）方案治疗，采用 2×2 伪因子随机化接受递增剂量甲氨蝶呤（MTX）而无亚叶酸解救加培门冬酰胺酶（C-MTX）或高剂量 MTX（HDMTX）联合亚叶酸解救。诱导后，中高危患者还随机接受或不接受奈拉滨的 6 个 5 天疗程。诱导失败的患者非随机接受 HDMTX 加奈拉滨。有明显中枢神经系统疾病（CNS3；白细胞计数≥5×109/L 伴原始细胞）的患者接受 HDMTX，并随机接受或不接受奈拉滨。除低危疾病患者外，所有患者均接受颅脑照射。
结果
5 年无事件生存率和总生存率分别为 83.7%±1.1%和 89.5%±0.9%。随机接受奈拉滨（n=323）和不接受奈拉滨（n=336）的 T-ALL 患者的 5 年无病生存率（DFS）分别为 88.2%±2.4%和 82.1%±2.7%（=0.029）。4 组间 DFS 差异有统计学意义（=0.01），MTX 和奈拉滨随机分组之间无交互作用（=0.41）。接受表现最佳的 C-MTX 加奈拉滨治疗的患者 5 年 DFS 为 91%（n=147）。接受奈拉滨治疗的患者与未接受奈拉滨治疗的患者相比，孤立性和联合性中枢神经系统复发明显减少（1.3%±0.63% vs 6.9%±1.4%；=0.0001）。所有 4 组的毒性反应包括神经毒性均可接受且相似。
结论
ABFM 治疗中加入奈拉滨可提高新诊断 T-ALL 儿童和青少年的 DFS，且不增加毒性。
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