Kantarjian Hagop, Aldoss Ibrahim, Jabbour Elias
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston.
Division of Leukemia, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, California.
JAMA Oncol. 2025 Jul 1;11(7):771-778. doi: 10.1001/jamaoncol.2025.0613.
Research in acute lymphoblastic leukemia (ALL) is translating into rapid changes in therapy and outcomes. Historically, adult ALL was treated with intensive chemotherapy extending over 2.5 to 3 years. This established tradition, accepted because of the high cure rates in childhood ALL, has been challenged by the development of highly active targeted therapies.
Treatment modalities, combined with less and shorter chemotherapy durations, have produced better results than chemotherapy. The novel therapies include using the more potent BCR::ABL1 tyrosine kinase inhibitors (eg, ponatinib, dasatinib) with the bispecific CD3-CD19 T-cell engager antibody blinatumomab in Philadelphia chromosome-positive ALL and combining blinatumomab and/or inotuzumab (CD22 antibody drug conjugate) with standard chemotherapy in B-cell ALL. These have been associated with improved 4-year survival rates of 85% to 90% in Philadelphia chromosome-positive ALL and 80% to 85% in B-cell ALL.
The management of ALL is changing rapidly. Investigators have evaluated frontline and later-line regimens with combinations of tyrosine kinase inhibitors and immunotherapies with less or no chemotherapy. Future research will evaluate CD19, CD20, and CD22 multitargeting antibodies and chimeric antigen receptor T-cell therapies, new antibody formulations, and less intensive/shorter regimens.
急性淋巴细胞白血病(ALL)的研究正在转化为治疗方法和治疗结果的快速变化。历史上,成人ALL采用持续2.5至3年的强化化疗进行治疗。由于儿童ALL的高治愈率而被接受的这一既定传统,已受到高活性靶向疗法发展的挑战。
与化疗相比,治疗方式结合更短疗程的化疗产生了更好的效果。新型疗法包括在费城染色体阳性ALL中使用更强效的BCR::ABL1酪氨酸激酶抑制剂(如波纳替尼、达沙替尼)与双特异性CD3-CD19 T细胞衔接抗体贝林妥欧单抗,以及在B细胞ALL中将贝林妥欧单抗和/或伊尼妥单抗(CD22抗体药物偶联物)与标准化疗联合使用。这些疗法与费城染色体阳性ALL中4年生存率提高至85%至90%以及B细胞ALL中4年生存率提高至80%至85%相关。
ALL的管理正在迅速变化。研究人员已经评估了酪氨酸激酶抑制剂和免疫疗法联合使用、化疗较少或无化疗的一线和二线治疗方案。未来的研究将评估CD19、CD20和CD22多靶点抗体以及嵌合抗原受体T细胞疗法、新的抗体配方以及强度较低/疗程较短的治疗方案。