帕纳替尼-博纳吐单抗或伊马替尼-化疗治疗成人费城染色体阳性急性淋巴细胞白血病。
完整摘要 · 中文译文
背景：随着酪氨酸激酶抑制剂和免疫疗法的使用，费城染色体阳性急性淋巴细胞白血病（Ph阳性ALL）的结局已显著改善。 方法：在本试验中，我们将成年Ph阳性ALL患者按2：1的比例随机分配，接受普纳替尼联合贝林妥欧单抗（干预组）或伊马替尼联合化疗（对照组）作为一线治疗。对照组中持续存在或再次出现可测量残留病的患者允许交叉至干预组。主要终点为无事件生存期。 结果：共有236例患者接受了随机分组：158例进入干预组，78例进入对照组。患者中位年龄为55岁（范围：24至82岁）。中位随访23.7个月时，干预组估计的24个月无事件生存率为86%，对照组为67%（P<0.001）。无可测量残留病灶的生存率分别为68%和42%。诱导治疗结束时，干预组94%的患者和对照组79%的患者观察到完全血液学缓解。博纳吐单抗巩固治疗后，分子学缓解率分别为71%和49%。交叉至干预组后，31例患者中有20例（64%）获得分子学缓解。总生存率在干预组为90%，在对照组为85%。累积复发率分别为5%和13%。截至本报告时，干预组仅19%的患者在首次完全血液学缓解后接受了造血干细胞移植。 结论：在这项3期试验中，一线无化疗的靶向及免疫治疗策略优于伊马替尼联合化疗。（由意大利癌症研究协会等资助；GIMEMA ALL2820，ClinicalTrials.gov编号：NCT04722848。）
完整摘要 · 英文原文
BACKGROUND: The outcome of Philadelphia-positive acute lymphoblastic leukemia (Ph-positive ALL) has greatly improved with the use of tyrosine kinase inhibitors and immunotherapy. METHODS: In this trial, we randomly assigned adult patients with Ph-positive ALL in a 2:1 ratio to receive ponatinib plus blinatumomab (intervention group) or imatinib plus chemotherapy (control group) as frontline treatment. A crossover to the intervention group was allowed for patients with persistence or reappearance of measurable residual disease in the control group. The primary end point was event-free survival. RESULTS: A total of 236 patients underwent randomization: 158 to the intervention group and 78 to the control group. The median age of the patients was 55 years (range, 24 to 82). At a median follow-up of 23.7 months, the estimated 24-month event-free survival was 86% in the intervention group and 67% in the control group (P<0.001). Survival with no measurable residual disease was 68% and 42%, respectively. At the end of induction, a complete hematologic response was observed in 94% of the patients in the intervention group and in 79% of those in the control group. After blinatumomab consolidation, a molecular response was observed in 71% and 49% of the patients, respectively. After crossover to the intervention group, 20 of 31 patients (64%) had a molecular response. Overall survival was 90% in the intervention group and 85% in the control group. The cumulative incidence of relapse was 5% and 13%, respectively. As of this report, only 19% of the patients in the intervention group had undergone hematopoietic stem-cell transplantation after having had a first complete hematologic response. CONCLUSIONS: In this phase 3 trial, a frontline chemotherapy-free targeted and immunotherapeutic approach was superior to the use of imatinib and chemotherapy. (Funded by Associazione Italiana per la Ricerca sul Cancro and others; GIMEMA ALL2820 ClinicalTrials.gov number, NCT04722848.).