Department of Hematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Sapienza, University of Rome, Rome, Italy.
Amgen Research (Munich) GmbH, Munich, Germany.
Blood Adv. 2022 Feb 8;6(3):1004-1014. doi: 10.1182/bloodadvances.2021005579.
The safety and efficacy of blinatumomab, a CD3/CD19-directed bispecific molecule, were examined in an open-label, single-arm, expanded access study (RIALTO). Children (>28 days and <18 years) with CD19+ relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R B-ALL) received up to 5 cycles of blinatumomab by continuous infusion (cycle: 4 weeks on/2 weeks off). The primary end point was incidence of adverse events. Secondary end points included complete response (CR) and measurable residual disease (MRD) response within the first 2 cycles and relapse-free survival (RFS), overall survival (OS), and allogeneic hematopoietic stem cell transplant (alloHSCT) after treatment. At final data cutoff (10 January 2020), 110 patients were enrolled (median age, 8.5 years; 88% had ≥5% baseline blasts). A low incidence of grade 3 or 4 cytokine release syndrome (n = 2; 1.8%) and neurologic events (n = 4; 3.6%) was reported; no blinatumomab-related fatal adverse events were recorded. The probability of response was not affected by the presence of cytogenetic/molecular abnormalities. Median OS was 14.6 months (95% confidence interval [CI]: 11.0-not estimable) and was significantly better for MRD responders vs MRD nonresponders (not estimable vs 9.3; hazard ratio, 0.18; 95% CI: 0.08-0.39). Of patients achieving CR after 2 cycles, 73.5% (95% CI: 61.4%-83.5%) proceeded to alloHSCT. One-year OS probability was higher for patients who received alloHSCT vs without alloHSCT after blinatumomab (87% vs 29%). These findings support the use of blinatumomab as a safe and efficacious treatment of pediatric R/R B-ALL. This trial was registered at www.clinicaltrials.gov as #NCT02187354.
blinatumomab 是一种靶向 CD3/CD19 的双特异性分子，在一项开放性、单臂、扩大准入研究（RIALTO）中检查了其安全性和疗效。≥28 天且＜18 岁的 CD19+复发/难治性 B 细胞前体急性淋巴细胞白血病（R/R B-ALL）患儿接受blinatumomab 连续输注（周期：4 周 ON/2 周 OFF），最多 5 个周期。主要终点是不良事件发生率。次要终点包括前 2 个周期内的完全缓解（CR）和可测量残留疾病（MRD）反应以及无复发生存（RFS）、总生存（OS）和治疗后异基因造血干细胞移植（alloHSCT）。在最终数据截止日期（2020 年 1 月 10 日），共纳入 110 例患者（中位年龄 8.5 岁；88%患者基线时有≥5%原始细胞）。报告了低发生率的 3 级或 4 级细胞因子释放综合征（n=2；1.8%）和神经系统事件（n=4；3.6%）；未记录到与 blinatumomab 相关的致命不良事件。反应率不受细胞遗传学/分子异常的影响。中位 OS 为 14.6 个月（95%置信区间[CI]：11.0-无法估计），MRD 应答者明显优于 MRD 无应答者（无法估计 vs 9.3；风险比，0.18；95%CI：0.08-0.39）。在 2 个周期后达到 CR 的患者中，73.5%（95%CI：61.4%-83.5%）接受 alloHSCT。在接受 alloHSCT 后与未接受 alloHSCT 后相比，blinatumomab 后 1 年 OS 概率更高（87% vs 29%）。这些发现支持将 blinatumomab 用作儿科 R/R B-ALL 的安全有效的治疗方法。该试验在 www.clinicaltrials.gov 上注册为#NCT02187354。
