Abstract

The management of Refractory/Relapsed B-cell Acute Lymphoblastic Leukemia (R/R ALL) remains challenging. Incorporating blinatumomab in R/R ALL treatment has shown encouraging results. We describe the outcome and predictors of response in children receiving blinatumomab as a bridge to definitive therapy. Immunoglobulin (Ig) G and viral serology before and after therapy were evaluated. Thirty-three patients that failed standard first-line treatments due to relapsed ALL (n = 22), persistent minimal residual disease (MRD) (n = 8), or refractory disease (n = 3) received blinatumomab. Grade 2 toxicity occurred in 27.2% of patients. MRD remission (<0.01%) was achieved in 72.7% of patients. Pre-blinatumomab absolute lymphocyte count (ALC) and MRD/ALC ratio significantly associated with MRD-response. Patients with t(1;19) translocation had lower response rate, compared to all other cytogenetic categories (p = 0.013). One-year event-free survival (EFS) and overall survival (OS) were 69.2% and 79.7%, respectively. Analysis of OS and EFS showed pre-blinatumomab MRD level, ALC, MRD/ALC ratio, t(1;19), and post-blinatumomab MRD remission associated with survival. Following blinatumomab, 83% (15/18) of tested patients had low IgG levels. IgG seronegative status was observed in 83% (12/15) for varicella zoster, 35% (6/17) for herpes zoster, 18% (3/17) for cytomegalovirus, and 26% (5/17) for Epstein Barr virus. Blinatumomab produced encouraging results in children with R/R ALL and low disease burden bridging to definitive therapy. Incorporating baseline genetics and biomarkers may help identify subgroups likely to be responsive/resistant to therapy. Viral serological testing pre- and post-blinatumomab is recommended to optimize supportive and preemptive therapy.

Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2022.2049936 .

摘要

难治性/复发性 B 细胞急性淋巴细胞白血病 (R/R ALL) 的管理仍然具有挑战性。将 blinatumomab 纳入 R/R ALL 治疗已显示出令人鼓舞的结果。我们描述了接受 blinatumomab 作为最终治疗的桥梁的儿童的结果和反应预测因子。评估了治疗前后的免疫球蛋白 (Ig) G 和病毒血清学。33 名因复发性 ALL ( n =  22)、持续性微小残留病 (MRD) ( n =  8) 或难治性疾病 ( n = 3）接受了blinatumomab。27.2% 的患者发生 2 级毒性。72.7% 的患者实现了 MRD 缓解（<0.01%）。博纳吐单抗前绝对淋巴细胞计数 (ALC) 和 MRD/ALC 比率与 MRD 反应显着相关。与所有其他细胞遗传学类别相比， t(1;19)易位患者的反应率较低 ( p =  0.013)。一年无事件生存期（EFS）和总生存期（OS）分别为69.2%和79.7%。OS 和 EFS 分析显示博纳吐单抗前 MRD 水平、ALC、MRD/ALC 比值、t(1;19)，以及与生存相关的博纳吐单抗后 MRD 缓解。博纳吐单抗后，83% (15/18) 的受试患者 IgG 水平较低。在 83% (12/15) 的水痘带状疱疹、35% (6/17) 的带状疱疹、18% (3/17) 的巨细胞病毒和 26% (5/17) 的 Epstein Barr 病毒中观察到 IgG 血清学阴性状态. Blinatumomab 在患有 R/R ALL 的儿童中产生了令人鼓舞的结果，并且疾病负担低，可以进行明确的治疗。结合基线遗传学和生物标志物可能有助于识别可能对治疗有反应/耐药的亚组。建议在博纳吐单抗前后进行病毒血清学检测，以优化支持性和先发制人的治疗。

本文的补充数据可在 https://doi.org/10.1080/08880018.2022.2049936 在线获取。