我如何治疗免疫治疗后复发的 B-ALL。
How I treat post-immunotherapy relapsed B-ALL.
发表日期：2024 Jul 24
作者：
Adam J Lamble, Alexandra E Kovach, Nirali N Shah
来源：
BLOOD
摘要：
尽管 B 细胞急性淋巴细胞白血病 (B-ALL) 的单抗原靶向治疗取得了重大进展，但无反应和复发仍然是主要挑战。 blinatumomab 或 CD19 定向嵌合抗原受体 T 细胞 (CD19-CAR) 后的抗原逃逸，如 CD19 阴性 B-ALL 或谱系转换 (LS) 至急性髓系白血病，呈现出诊断和治疗的复杂性。鉴于输注后复发的患者，特别是那些靶抗原丢失的患者，预后不佳，因此必须采取战略性的诊断和治疗方法。在本次讨论中，我们概述了管理免疫治疗后事件的系统方法，按 CD19 阳性复发、CD19 阴性复发和 LS 进行分类。我们探索的治疗方式包括 CD19-CAR 回输、人源化 CAR 构建体、组合策略和替代抗原靶向疗法，例如 blinatumomab 和 inotuzumab。解决了诊断中的挑战，特别是抗原逃逸方面的挑战，强调了下一代测序和多参数流式细胞术在骨髓标记物监测中的作用。版权所有 © 2024 美国血液学会。
Despite significant advancements in single-antigen targeted therapies for B-cell acute lymphoblastic leukemia (B-ALL), non-response and relapse persist as major challenges. Antigen escape following blinatumomab or CD19-directed chimeric antigen receptor T cells (CD19-CAR), as CD19-negative B-ALL or lineage switch (LS) to acute myeloid leukemia, present diagnostic and treatment complexities. Given the poor outcomes for patients experiencing a post-infusion relapse, particularly those with loss of the target antigen, a strategic approach to diagnosis and treatment is imperative. In this discussion, we outline a systematic approach to managing post-immunotherapy events, categorized by CD19-positive relapse, CD19-negative relapse, and LS. We explore treatment modalities including CD19-CAR re-infusions, humanized CAR constructs, combinatorial strategies, and alternative antigen-targeted therapies, such as blinatumomab and inotuzumab. Challenges in diagnosis, particularly with antigen-escape, are addressed, highlighting the role of next-generation sequencing and multiparameter flow cytometry for myeloid marker monitoring.Copyright © 2024 American Society of Hematology.