The Care and Cure of the Leukemias in 2026

医学 嵌合抗原受体 髓系白血病 白血病 慢性淋巴细胞白血病 靶向治疗 免疫疗法 单克隆抗体 免疫学 酪氨酸激酶 肿瘤科 预期寿命 髓样 癌症研究 造血 微小残留病 疾病 CD33 布鲁顿酪氨酸激酶 免疫毒素 Blinatumoab公司 酪氨酸激酶抑制剂 单克隆 干细胞 抗原 造血干细胞移植 CD19 移植 化疗 威尼斯人 生活质量(医疗保健) 急性淋巴细胞白血病
作者
Hagop Kantarjian,Helen T. Chifotides,F. Haddad,Elias Jabbour,Nitin Jain,Tapan Kadia,Farhad Ravandi,Mary Alma Welch,William Wierda,E. J. Freireich
出处
期刊:American Journal of Hematology [Wiley]
卷期号:101 (4): 807-831
标识
DOI:10.1002/ajh.70247
摘要

It is an exciting era in leukemia owing to the development of novel targeted therapies and advances in genomics, pathophysiology, prognostication, and monitoring (e.g., highly sensitive measurable residual disease assays). Currently, most leukemias are effectively treated with immunotherapies (highly effective monoclonal antibodies targeting CD19 [blinatumomab], or CD22 [inotuzumab ozogamicin]), BCR::ABL1 tyrosine kinase inhibitors (TKIs; e.g., dasatinib, ponatinib), Bruton TKIs (e.g., ibrutinib, acalabrutinib), BCL-2 inhibitors (venetoclax), IDH1/2 inhibitors (ivosidenib, olutasidenib, and enasidenib), FLT3 inhibitors (e.g., midostaurin, quizartinib, and gilteritinib), menin inhibitors (revumenib, ziftomenib), and chimeric antigen receptor T-cell therapies. These novel agents and their judicious use in combination strategies have transformed the treatment landscape across all leukemias, significantly increased survival and quality of life for patients, and attenuated the need for intensive chemotherapy and hematopoietic stem cell transplantation. Leukemia subtypes, such as Philadelphia-positive acute lymphoblastic leukemia (incurable before 2000) and chronic lymphocytic leukemia (previously considered incurable) with historically dire prognoses were recently transformed to favorable leukemias with 5- and 10-year survival rates of 80+% and 90+%, respectively. The BCR::ABL1 TKIs resulted in normal life expectancy in chronic myeloid leukemia. Notable advances have also been made in AML with targeted therapies, although some subsets (older/unfit patients for intensive chemotherapy, complex karyotype, TP53-mutated, KMT2A-rearranged, and treated secondary AML) still have unfavorable outcomes. Herein, we provide a high-level overview of prominent clinical developments across all leukemias. In contemporary times, harnessing the benefits of novel targeted therapies and the evolving treatment landscape bolster the optimistic view that most, if not all, leukemias are curable.
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