Department of Hematology, University Hospital Schleswig-Holstein , Campus Kiel, Kiel, Germany.
Institute of Immunology, University Hospital Schleswig-Holstein , Campus Kiel, Kiel, Germany.
Expert Rev Hematol. 2020 Nov;13(11):1211-1233. doi: 10.1080/17474086.2020.1831380. Epub 2020 Nov 4.
Blinatumomab, first in a class of bispecific T-cell engagers, revolutionized treatment paradigm of B-cell precursor relapsed/refractory or minimal residual disease positive acute lymphoblastic leukemia (ALL) in adults and children, inducing deep remissions in a proportion of patients. However, significant numbers of patients do not respond or eventually relapse. Strategies for improvement of treatment outcomes are required.
This review discusses the main structural and functional features of blinatumomab, and its place in the treatment of ALL. Furthermore, prospects to increase the efficacy of blinatumomab are addressed. The developments in the field of bispecific antibodies and their possible implications for treatment of ALL are reviewed.
Better understanding the mechanisms of response and resistance to blinatumomab might help us to identify the group of patients benefiting most from treatment and to spare potentially toxic subsequent treatment strategies. Data emerging from ongoing clinical trials might change the treatment landscape of ALL and beyond. Early use of blinatumomab in frontline protocols with more advantageous treatment sequences and in combination with other targeted therapies might reduce the failure rates. Exponentially increasing number of novel treatment options and their possible combinations might complicate treatment decision-making without data from randomized trials.
blinatumomab 是首个双特异性 T 细胞衔接器类药物，彻底改变了成人和儿童复发性/难治性或微小残留病阳性急性淋巴细胞白血病 (ALL) 的治疗模式，使一部分患者产生深度缓解。然而，仍有相当数量的患者无反应或最终复发。需要采取策略来改善治疗效果。
本文讨论了 blinatumomab 的主要结构和功能特征及其在 ALL 治疗中的地位。此外，还探讨了提高 blinatumomab 疗效的前景。综述了双特异性抗体领域的发展及其对 ALL 治疗的可能影响。
更好地了解对 blinatumomab 的反应和耐药机制，可能有助于我们确定最受益于治疗的患者群体，并避免潜在的毒性后续治疗策略。来自正在进行的临床试验的数据可能会改变 ALL 及其他疾病的治疗格局。在一线方案中早期使用 blinatumomab，采用更有利的治疗顺序，并与其他靶向治疗联合使用，可能会降低失败率。新型治疗选择的数量呈指数级增长，并且可能会增加其组合，这可能会使治疗决策变得复杂，而没有随机试验的数据。
