Onco Hematology, Department of Oncology, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy.
IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
Expert Opin Biol Ther. 2023 Feb;23(2):175-194. doi: 10.1080/14712598.2023.2174015. Epub 2023 Feb 14.
The introduction of target molecules and immunological therapies is changing the treatment landscape of acute myeloid leukemia (AML).
We recapitulate the biological therapies that can be employed in the treatment of elderly patients with AML. Alongside small molecules inhibitors that target specific gene mutations, antibodies, tumor microenvironment modulators, and cellular therapies are being developed for the cure of the disease. Here, we report the biological activities, the efficacy and toxicities of humanized antibodies and antibody-drug conjugates that targets surface antigens as CD33 (gemtuzumab ozogamicine) or CD123 (pivekimab sunirine). We further explore mechanisms and effectiveness of medications that modify the microenvironment, such as glasdegib, or that harness the immune system against leukemia, such as CD47 antibody magrolimab, PD1/PDL1 inhibitors pembrolizumab and nivolumab, TIM3 inhibitor sabatolimab, T-cell and NK-cell engagers. Cellular therapies are considered, even if a large trial is still pending for the feasibility of the approach. In this scenario, a brief overview of the mechanism of action of target agents is provided, particularly with respect to their biological mechanisms.
Overall, this therapeutic armamentarium will constitute the basis for multimodal and personalized combinations that, in the idea of precision medicine, will enormously benefit elderly AML patients.
靶向分子和免疫疗法的引入正在改变急性髓系白血病(AML)的治疗格局。
我们回顾了可用于治疗老年 AML 患者的生物疗法。除了针对特定基因突变的小分子抑制剂外,还在开发针对肿瘤微环境调节剂和细胞疗法的抗体,以治愈该疾病。在这里,我们报告了针对表面抗原(如 CD33(吉妥珠单抗奥佐米星)或 CD123(pivekimab sunirine))的人源化抗体和抗体药物偶联物的生物学活性、疗效和毒性。我们进一步探讨了改变微环境的药物(如 glasdegib)或利用免疫系统对抗白血病的药物(如 CD47 抗体 magrolimab、PD1/PDL1 抑制剂 pembrolizumab 和 nivolumab、TIM3 抑制剂 sabatolimab、T 细胞和 NK 细胞衔接器)的机制和有效性。细胞疗法也被考虑在内,尽管一项大型试验仍在等待该方法的可行性。在这种情况下,提供了针对目标药物的作用机制的简要概述,特别是针对其生物学机制。
总体而言,这种治疗武器将构成多模式和个性化组合的基础,在精准医学的理念下,这将使老年 AML 患者极大受益。