Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA.
Department of Medicine and Comprehensive Cancer Center, University of Chicago, Chicago, IL.
Blood Adv. 2018 Jul 10;2(13):1522-1531. doi: 10.1182/bloodadvances.2018019034.
In the phase 3 TOWER study, blinatumomab demonstrated an overall survival benefit over standard-of-care chemotherapy (SOC) in adults with relapsed or refractory (r/r) Philadelphia chromosome-negative (Ph) B-precursor acute lymphoblastic leukemia (ALL). Nearly all patients in both treatment arms experienced an adverse event (AE), and the incidence rate of serious AEs was higher for blinatumomab. However, as treatment exposure differed between the 2 arms, we conducted an exploratory safety analysis comparing exposure-adjusted event rates (EAERs) of blinatumomab vs SOC. Analyses were conducted for all patients who received therapy (safety population). Patients received a median (range) of 2 cycles (1-9) of blinatumomab (N = 267) vs 1 cycle (1-4) of SOC (N = 109). Grade ≥3 AE rates were generally higher in cycle 1 of blinatumomab than in cycle 2 (76% vs 37%). After adjusting for time on treatment, EAERs of grade ≥3 were significantly lower for blinatumomab vs SOC overall (10.73 vs 45.27 events per patient-year; < .001) and for events of clinical interest, including infections (1.63 vs 6.49 events per patient-year; < .001), cytopenias (3.64 vs 20.07 events per patient-year; < .001), and neurologic events (0.38 vs 0.95 events per patient-year; = .008). The EAER of grade ≥3 cytokine-release syndrome was higher for blinatumomab than for SOC (0.16 vs 0 events per patient-year; = .038). These data further support the role of blinatumomab as an efficacious and well-tolerated treatment option for patients with r/r Ph ALL. This trial was registered at www.clinicaltrials.gov as #NCT02013167.
在 3 期 TOWER 研究中，blinatumomab 与标准治疗化疗（SOC）相比，在费城染色体阴性（Ph）B 前体急性淋巴细胞白血病（ALL）的复发/难治性（r/r）成人中显示出总体生存获益。两个治疗组的几乎所有患者均经历了不良事件（AE），blinatumomab 的严重 AE 发生率更高。然而，由于两个治疗组之间的治疗暴露存在差异，我们进行了一项探索性安全性分析，比较了 blinatumomab 与 SOC 的暴露调整事件率（EAER）。分析针对所有接受治疗的患者进行（安全性人群）。患者接受了中位数（范围）为 2 个周期（1-9）的 blinatumomab（N=267）与 1 个周期（1-4）的 SOC（N=109）。blinatumomab 第 1 周期的≥3 级 AE 发生率一般高于第 2 周期（76%比 37%）。在调整治疗时间后，blinatumomab 的 EAER 显著低于 SOC 总体（10.73 比 45.27 个患者-年事件；<.001），以及临床关注的事件，包括感染（1.63 比 6.49 个患者-年事件；<.001）、细胞减少症（3.64 比 20.07 个患者-年事件；<.001）和神经事件（0.38 比 0.95 个患者-年事件；=.008）。blinatumomab 的≥3 级细胞因子释放综合征的 EAER 高于 SOC（0.16 比 0 个患者-年事件；=0.038）。这些数据进一步支持 blinatumomab 作为复发/难治性 Ph ALL 患者有效且耐受良好的治疗选择的作用。该试验在 www.clinicaltrials.gov 上注册，编号为 #NCT02013167。
