Mohamed Jiffry Mohamed Zakee, Kloss Robert, Ahmed-Khan Mohammad, Carmona-Pires Felipe, Okam Nkechi, Weeraddana Prabasha, Dharmaratna Dinusha, Dandwani Mehndi, Moin Kayvon
Department of Internal Medicine, Danbury Hospital, Danbury, CT, USA.
Department of Hematology & Oncology, Danbury Hospital, Danbury, CT, USA.
Hematology. 2023 Dec;28(1):2196482. doi: 10.1080/16078454.2023.2196482.
Acute myeloid leukemia [AML] is a heterogenous group of primary hematopoietic neoplasms arising from myeloid precursor cells. Up to 50% of patients failed to achieve remission with initial therapy and go on to develop refractory AML. Whenever possible, enrollment in a clinical trial in view of the paucity of evidence surrounding a clearly superior treatment modality is recommended, and the therapy which provides the best chance for cure post remission is allogeneic hematopoietic stem cell transplantation [HCT], with much of everyday clinical decision-making in relapsed/refractory (R/R) AML surrounding the choice of the least toxic regimen that could achieve remission and enable prompt HCT.
We discuss a variety of treatment modalities employed in the R/R AML setting beginning with traditional cytotoxic regimens. We then turn our attention to targeted therapies that have shown efficacy in specific patient populations such as the IDH inhibitors and FLT3 inhibitors and lastly, we turn our attention to immunotherapeutic agents employed in the R/R in the setting, such as CD33 inhibitors and bispecific antibodies.
It appears increasingly clear that approaching AML as a homogenous disease entity is unsatisfactory in view of the variations in such disease factors as cytogenetic and molecular markers, age, and disease severity at presentation; all of which contribute significantly to heterogeneity of the disease. Moving forward, treating AML would likely require tailored therapy following advances in technology such as molecular profiling, drug sensitivity and resistance testing.
急性髓系白血病(AML)是一组起源于髓系前体细胞的异质性原发性造血肿瘤。高达50%的患者初始治疗未能达到缓解,进而发展为难治性AML。鉴于围绕明显更优治疗方式的证据匮乏,只要有可能,建议参加临床试验,而缓解后提供最佳治愈机会的治疗方法是异基因造血干细胞移植(HCT),复发性/难治性(R/R)AML的日常临床决策大多围绕选择毒性最小且能实现缓解并使及时进行HCT成为可能的方案。
我们从传统细胞毒性方案开始讨论R/R AML环境中采用的各种治疗方式。然后我们将注意力转向在特定患者群体中显示出疗效的靶向治疗,如异柠檬酸脱氢酶(IDH)抑制剂和FMS样酪氨酸激酶3(FLT3)抑制剂,最后,我们将注意力转向R/R环境中使用的免疫治疗药物,如CD33抑制剂和双特异性抗体。
鉴于细胞遗传学和分子标志物、年龄以及就诊时疾病严重程度等疾病因素存在差异,将AML视为一种同质疾病实体的做法似乎越来越不能令人满意;所有这些因素都对疾病的异质性有显著影响。展望未来,随着分子谱分析、药物敏感性和耐药性测试等技术的进步,治疗AML可能需要量身定制的疗法。