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Abstract：
BACKGROUND: Many older adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) have a relapse despite having a measurable residual disease (MRD)-negative complete remission with combination chemotherapy. The addition of blinatumomab, a bispecific T-cell engager molecule that is approved for the treatment of relapsed, refractory, and MRD-positive BCP-ALL, may have efficacy in patients with MRD-negative remission.
METHODS: In a phase 3 trial, we randomly assigned patients 30 to 70 years of age with BCR::ABL1-negative BCP-ALL (with :: indicating fusion) who had MRD-negative remission (defined as <0.01% leukemic cells in bone marrow as assessed on flow cytometry) after induction and intensification chemotherapy to receive four cycles of blinatumomab in addition to four cycles of consolidation chemotherapy or to receive four cycles of consolidation chemotherapy alone. The primary end point was overall survival, and relapse-free survival was a secondary end point.
RESULTS: The data and safety monitoring committee reviewed the results from the third efficacy interim analysis and recommended that they be reported. Complete remission with or without full count recovery was observed in 395 of 488 enrolled patients (81%). Of the 224 patients with MRD-negative status, 112 were assigned to each group. The characteristics of the patients were balanced between the groups. At a median follow-up of 43 months, an advantage was observed in the blinatumomab group as compared with the chemotherapy-only group with regard to overall survival (at 3 years: 85% vs. 68%; hazard ratio for death, 0.41; 95% confidence interval [CI], 0.23 to 0.73; P = 0.002), and the 3-year relapse-free survival was 80% with blinatumomab and 64% with chemotherapy alone (hazard ratio for relapse or death, 0.53; 95% CI, 0.32 to 0.87). A higher incidence of neuropsychiatric events was reported in the blinatumomab group than in the chemotherapy-only group.
CONCLUSIONS: The addition of blinatumomab to consolidation chemotherapy in adult patients in MRD-negative remission from BCP-ALL significantly improved overall survival. (Funded by the National Institutes of Health and others; E1910 ClinicalTrials.gov number, NCT02003222.).
METHODS: In a phase 3 trial, we randomly assigned patients 30 to 70 years of age with BCR::ABL1-negative BCP-ALL (with :: indicating fusion) who had MRD-negative remission (defined as <0.01% leukemic cells in bone marrow as assessed on flow cytometry) after induction and intensification chemotherapy to receive four cycles of blinatumomab in addition to four cycles of consolidation chemotherapy or to receive four cycles of consolidation chemotherapy alone. The primary end point was overall survival, and relapse-free survival was a secondary end point.
RESULTS: The data and safety monitoring committee reviewed the results from the third efficacy interim analysis and recommended that they be reported. Complete remission with or without full count recovery was observed in 395 of 488 enrolled patients (81%). Of the 224 patients with MRD-negative status, 112 were assigned to each group. The characteristics of the patients were balanced between the groups. At a median follow-up of 43 months, an advantage was observed in the blinatumomab group as compared with the chemotherapy-only group with regard to overall survival (at 3 years: 85% vs. 68%; hazard ratio for death, 0.41; 95% confidence interval [CI], 0.23 to 0.73; P = 0.002), and the 3-year relapse-free survival was 80% with blinatumomab and 64% with chemotherapy alone (hazard ratio for relapse or death, 0.53; 95% CI, 0.32 to 0.87). A higher incidence of neuropsychiatric events was reported in the blinatumomab group than in the chemotherapy-only group.
CONCLUSIONS: The addition of blinatumomab to consolidation chemotherapy in adult patients in MRD-negative remission from BCP-ALL significantly improved overall survival. (Funded by the National Institutes of Health and others; E1910 ClinicalTrials.gov number, NCT02003222.).
摘要：
背景：许多患有B细胞前体急性淋巴细胞白血病（BCP-ALL）的老年人尽管通过联合化疗可测量的残留病（MRD）阴性完全缓解，但仍有复发。Blinatumomab的加入，一种双特异性T细胞衔接分子，被批准用于治疗复发，耐火材料,和MRD阳性BCP-ALL,MRD阴性缓解患者可能有疗效。
方法：在一项3期试验中，我们将30~70岁的BCR::ABL1阴性BCP-ALL(提示融合)患者随机分组,这些患者在诱导和强化化疗后MRD阴性缓解(定义为流式细胞术评估骨髓中白血病细胞<0.01%),除了接受4个周期的巩固化疗外,还接受4个周期的blinatumomab治疗或单独接受4个周期的巩固化疗.主要终点是总生存期,无复发生存期是次要终点.
结果：数据和安全监测委员会审查了第三次疗效中期分析的结果，并建议将其报告。在488例登记患者中，有395例（81%）观察到有或没有完全恢复的完全缓解。在224例MRD阴性患者中，每组分配112个。患者的特征在组间平衡。中位随访时间为43个月,与仅化疗组相比，blinatumomab组在总生存率方面具有优势（3年时：85%与68%；死亡危险比，0.41；95%置信区间[CI]，0.23至0.73；P=0.002），3年无复发生存率为80%，而博纳吐单抗为64%，单独化疗为64%（复发或死亡的风险比，0.53；95%CI，0.32至0.87）。据报道，博纳图莫组的神经精神事件发生率高于单纯化疗组。
结论：BCP-ALLMRD阴性缓解的成年患者在巩固化疗中加入blinatumomab可显着提高总生存率。（由美国国立卫生研究院和其他机构资助；E1910ClinicalTrials.gov编号，NCT02003222。).
方法：在一项3期试验中，我们将30~70岁的BCR::ABL1阴性BCP-ALL(提示融合)患者随机分组,这些患者在诱导和强化化疗后MRD阴性缓解(定义为流式细胞术评估骨髓中白血病细胞<0.01%),除了接受4个周期的巩固化疗外,还接受4个周期的blinatumomab治疗或单独接受4个周期的巩固化疗.主要终点是总生存期,无复发生存期是次要终点.
结果：数据和安全监测委员会审查了第三次疗效中期分析的结果，并建议将其报告。在488例登记患者中，有395例（81%）观察到有或没有完全恢复的完全缓解。在224例MRD阴性患者中，每组分配112个。患者的特征在组间平衡。中位随访时间为43个月,与仅化疗组相比，blinatumomab组在总生存率方面具有优势（3年时：85%与68%；死亡危险比，0.41；95%置信区间[CI]，0.23至0.73；P=0.002），3年无复发生存率为80%，而博纳吐单抗为64%，单独化疗为64%（复发或死亡的风险比，0.53；95%CI，0.32至0.87）。据报道，博纳图莫组的神经精神事件发生率高于单纯化疗组。
结论：BCP-ALLMRD阴性缓解的成年患者在巩固化疗中加入blinatumomab可显着提高总生存率。（由美国国立卫生研究院和其他机构资助；E1910ClinicalTrials.gov编号，NCT02003222。).
