Università Statale di Milano, Milan and Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy.
Institut Universitaire du Cancer, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
Blood Adv. 2020 Apr 14;4(7):1518-1525. doi: 10.1182/bloodadvances.2019000874.
In a phase 3 clinical study of heavily pretreated adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL), overall survival (OS) following blinatumomab, a BiTE (bispecific T-cell engager) immunooncology therapy, was significantly improved vs chemotherapy following induction (cycles 1 to 2). Here we report the efficacy and safety of those who received additional cycles of blinatumomab. Blinatumomab was administered as a continuous IV infusion for 4 weeks in a 6-week cycle. Patients who achieved a bone marrow response (≤5% blasts) or complete remission (full, partial, or incomplete hematological recovery) during induction could receive additional cycles of blinatumomab. OS and relapse-free survival (RFS) for consolidation (cycles 3 to 5) vs no consolidation, and maintenance (cycles ≥6) vs no maintenance were analyzed using Simon-Makuch and Mantel-Byar odds ratios. Of 267 patients who received blinatumomab induction, 86 (32%) entered consolidation and 36 (13%) entered maintenance. Evidence of longer OS was demonstrated among the maintenance group compared with no-maintenance (median OS [95% confidence interval, CI]: not reached for maintenance vs 15.5 months for no maintenance). Median RFS (months; 95% CI) was numerically longer among maintenance group (14.5; 7.1 to 21.9) compared with no-maintenance (9.8; 8.5 to 11.1). A lower incidence of adverse events was seen during maintenance (72.2%) compared with induction (97.2%) and consolidation (86.1%). Adults with R/R ALL who achieved remission following blinatumomab induction had longer survival on continuation therapy than those who discontinued blinatumomab early, supporting the use of blinatumomab as long-term therapy. No new safety signals were reported. This trial was registered at www.clinicaltrials.gov as #NCT02013167.
在一项针对复发/难治性（R/R）急性淋巴细胞白血病（ALL）成人患者的 3 期临床研究中，与诱导后接受化疗相比，blinatumomab（一种双特异性 T 细胞衔接免疫肿瘤学疗法）治疗后的总生存期（OS）显著改善。在此，我们报告了那些接受额外blinatumomab 周期治疗的患者的疗效和安全性。blinatumomab 以连续静脉输注的方式在 6 周的周期中给药 4 周。在诱导期间达到骨髓反应（≤5%blasts）或完全缓解（完全、部分或不完全血液学恢复）的患者可以接受额外的blinatumomab 周期治疗。采用 Simon-Makuch 和 Mantel-Byar 优势比分析巩固（周期 3 至 5）与未巩固、维持（周期≥6）与未维持的 OS 和无复发生存率（RFS）。在接受blinatumomab 诱导的 267 例患者中，86 例（32%）进入巩固期，36 例（13%）进入维持期。与未维持组相比，维持组的 OS 证据更长（中位 OS[95%置信区间，CI]：未达到维持组 vs 无维持组 15.5 个月）。维持组的中位 RFS（月；95%CI）也长于无维持组（14.5；7.1 至 21.9）。与诱导（97.2%）和巩固（86.1%）相比，维持组的不良事件发生率较低（72.2%）。在blinatumomab 诱导后达到缓解的 R/R ALL 成人患者在继续治疗中的生存时间长于早期停止使用 blinatumomab 的患者，支持将 blinatumomab 作为长期治疗。未报告新的安全性信号。该试验在 www.clinicaltrials.gov 上注册为 #NCT02013167。
