肿瘤细胞治疗研究
英文原题:Upfront Immunotherapy Approaches in the Management of Adults with Acute Lymphoblastic Leukemia.
Upfront Immunotherapy Approaches in the Management of Adults with Acute Lymphoblastic Leukemia.
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成人B细胞前体急性淋巴细胞白血病(BCP-ALL)的治疗格局正在发生范式转变,推动因素是免疫疗法“无化疗”和“轻化疗”方案的发展。这些策略旨在降低毒性的同时保持高疗效,对可能无法耐受强化化疗的老年患者尤为重要。对于费城染色体阳性(Ph+)BCP-ALL,将ABL酪氨酸激酶抑制剂(TKI)与blinatumomab(CD3/CD19双特异性T细胞衔接器)联合使用显示出显著疗效;部分研究报告分子缓解率达90%–100%,长期生存率超过80%,且无需强化化疗或异基因造血细胞移植(allo-HCT)。
对于费城染色体阴性(Ph−)BCP-ALL,基于免疫疗法的blinatumomab与inotuzumab ozogamicin(抗CD22抗体药物偶联物)联合方案可带来较高完全缓解率和可测量微小残留病(MRD)阴性率,且毒性可管理。嵌合抗原受体(CAR)T细胞疗法仍是治疗复发/难治性B-ALL的变革性选择,但将其纳入一线治疗仍在研究中。目前试验正在评估这些药物的最佳序贯和联合方案,以及其能否使部分患者免于化疗和/或allo-HCT。随着证据不断积累,“无化疗”和“轻化疗”方案——通过将最低限度化疗与靶向药物相结合,在疗效与毒性降低之间取得平衡——有望重新定义成人BCP-ALL的标准治疗,为实现持久缓解并减少治疗相关发病率提供可能。
The therapeutic landscape of adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is undergoing a paradigm shift, driven by the development of immunotherapy-based "chemo-free" and "chemo-light' regimens. These strategies aim to achieve high efficacy with reduced toxicity, particularly in older adults who may not tolerate intensive chemotherapy. In Philadelphia chromosome-positive (Ph+) BCP-ALL, the incorporation of ABL tyrosine kinase inhibitors (TKIs) with blinatumomab (CD3/CD19 bispecific T-cell engager) has shown remarkable efficacy, with some studies reporting molecular response rates in the range of 90-100% and long-term survival exceeding 80% without the need for intensive chemotherapy or allogeneic hematopoietic cell transplantation (allo-HCT).
In Philadelphia-negative (Ph-) BCP- ALL, an immunotherapy-based combination of blinatumomab and inotuzumab ozogamicin (anti-CD22 antibody-drug conjugate) has demonstrated high rates of complete remission and measurable residual disease (MRD) negativity, with manageable toxicity. While chimeric antigen receptor (CAR) T-cell therapy remains a transformative option for relapsed/refractory B-ALL, its integration into frontline treatment is still under investigation.
Ongoing trials are evaluating the optimal sequencing and combinations of these agents and their potential to obviate the need for chemotherapy and/or allo-HCT in selected patients. As evidence continues to accumulate, chemo-free and chemo-light regimens, incorporating minimal chemotherapy with targeted agents to balance efficacy and reduced toxicity, are poised to redefine the standard of care for adults BCP-ALL, offering the possibility of durable remissions with reduced treatment-related morbidity.
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