抗 CD22/CD19 CAR-T 细胞疗法 CART2219.1 在成人和儿童复发/难治性 B-ALL 中的 I/II 期试验
A Phase I/II Trial of Anti-CD22/CD19 CAR-T Cell Therapy, CART2219.1, in Adult and Pediatric Relapsed/Refractory B-ALL.
在一项多中心I/II期试验中,所有患者(n=11;7名儿童,4名成人)在第28天均达到完全缓解(91%为微小残留病阴性)。
英文原题:Outcome of second allogeneic hematopoietic cell transplantation in adult patients with relapsed B-cell acute lymphoblastic leukemia in the era of new immunotherapeutic agents.
Outcome of second allogeneic hematopoietic cell transplantation in adult patients with relapsed B-cell acute lymphoblastic leukemia in the era of new immunotherapeutic agents.
费城染色体(Ph)阴性B-ALL(n = 45)接受新型药物治疗,与常规化疗相比显示出改善的生存结局(中位生存期29.6 vs.
异基因造血细胞移植(allo-HCT)仍被推荐为复发B细胞急性淋巴细胞白血病(ALL)的标准治疗选择。关于第二次allo-HCT(allo-HCT2),既往allo-HCT后不同的合并症和白血病演变可能影响较差的生存结局。随着包括blinatumomab、inotuzumab ozogamicin和ponatinib在内的新型免疫治疗药物的引入,我们获得了更多进行allo-HCT2的机会,期待更有利的移植结局。我们分析了78例接受allo-HCT2的移植后复发B-ALL成人患者。费城染色体(Ph)阴性B-ALL(n = 45)接受新型药物治疗的患者与常规化疗相比显示出改善的生存结局(中位生存期29.6 vs. 6.8个月,p = 0.018),这主要由较低的5年累积复发率驱动(37.9% vs. 68.8%,p = 0.037)。相反,在Ph阳性B-ALL(n = 33)中未观察到allo-HCT2的生存优势,各挽救方案的中位生存期为16.0个月。我们的发现强调了新型挽救治疗在Ph阴性B-ALL中的疗效,同时强调了Ph阳性ALL需要替代策略。总体而言,allo-HCT2后的复发仍然具有挑战性,这强调需要除allo-HCT3之外的策略,包括新型药物如嵌合抗原受体(CAR)-T/NK疗法或移植后微小残留病靶向治疗。
Allogeneic hematopoietic cell transplantation (allo-HCT) is still recommended as a standard treatment of choice for relapsed B-cell acute lymphoblastic leukemia (ALL). Regarding the second allo-HCT (allo-HCT2), variable comorbid conditions and leukemic evolution after previous allo-HCT may affect poor survival outcomes. With the introduction of newer immunotherapeutic agents including blinatumomab, inotuzumab ozogamicin, and ponatinib, we got more chances for allo-HCT2 expecting more promising transplantation outcomes. We analyzed 78 adult patients with post-HCT relapsed B-ALL undergoing allo-HCT2. Philadelphia chromosome (Ph)-negative B-ALL (n = 45) treated with nower agents showed improved survival outcomes compared to conventional chemotherapy (median survival 29.6 vs. 6.8 months, p = 0.018), which was primarily driven by lower 5-year cumulative incidence of relapse (37.9% vs. 68.8%, p = 0.037). In contrast, no survival advantage of allo-HCT2 was observed in Ph-positive B-ALL (n = 33) with a median survival of 16.0 months across the salvage regimens. Our findings highlighted the efficacy of newer salvage therapies in Ph-negative B-ALL, while underscores the need for alternative strategies for Ph-positive ALL. Overall, relapses after allo-HCT2 are still challenging which emphasize the need for strategies other than allo-HCT3 including newer agents such as chimeric antigen receptor (CAR)-T/NK therapies or post-transplant minimal residual disease targeted therapies.
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