CELL INTELLIGENCE · 肿瘤细胞治疗研究

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.