CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Blinatumomab Prior to CAR-T Cell Therapy-A Treatment Option Worth Consideration for High Disease Burden.
Blinatumomab Prior to CAR-T Cell Therapy-A Treatment Option Worth Consideration for High Disease Burden.
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在儿童复发/难治性B细胞前体急性淋巴细胞白血病(r/r BCP-ALL)中,CAR-T 细胞输注前的最佳桥接治疗仍是一个未解决的问题。在CAR-T 治疗前使用blinatumomab存在争议,因为CD19+靶细胞的潜在丢失可能对随后使用的CAR-T 细胞的激活、持久性以及由此产生的疗效产生负面影响。
在此,我们报告了单中心经验,7例化疗难治性BCP-ALL患儿在CAR-T 细胞治疗前接受blinatumomab治疗,其中6例用于在单采前降低疾病负荷,2例作为桥接治疗。除1例外,所有患者均对blinatumomab有反应。在CAR-T 细胞输注时,所有患者均处于细胞学完全缓解(CR)。4例患者PCR-MRD低阳性,其余3例为MRD阴性。CAR-T 输注后第+28天,所有患者均保持CR,7例患者中有6例为MRD阴性。中位随访497天时,4例患者仍处于CR且MRD阴性。3例患儿以CD19阴性疾病复发:其中2例死亡,1例既往对blinatumomab无反应者通过干细胞移植成功挽救。
总之,blinatumomab可有效降低疾病负荷,且副作用少于标准化疗药物。因此,对于CAR-T 细胞治疗前高疾病负荷的患者,这可能是一个有效的选择,且没有明确证据表明会损害疗效;然而,仍需进一步研究。
The optimal bridging therapy before CAR-T cell infusion in pediatric relapsed or refractory B-cell precursor acute lymphoblastic leukemia (r/r BCP-ALL) still remains an open question. The administration of blinatumomab prior to CAR-T therapy is controversial since a potential loss of CD19+ target cells may negatively impact the activation, persistence, and, as a consequence, the efficacy of subsequently used CAR-T cells.
Here, we report a single-center experience in seven children with chemorefractory BCP-ALL treated with blinatumomab before CAR-T cell therapy either to reduce disease burden before apheresis (six patients) or as a bridging therapy (two patients). All patients responded to blinatumomab except one. At the time of CAR-T cell infusion, all patients were in cytological complete remission (CR). Four patients had low positive PCR-MRD, and the remaining three were MRD-negative.
All patients remained in CR at day +28 after CAR-T infusion, and six out of seven patients were MRD-negative. With a median follow-up of 497 days, four patients remain in CR and MRD-negative. Three children relapsed with CD19 negative disease: two of them died, and one, who previously did not respond to blinatumomab, was successfully rescued by stem cell transplant. To conclude, blinatumomab can effectively lower disease burden with fewer side effects than standard chemotherapeutics.
Therefore, it may be a valid option for patients with high-disease burden prior to CAR-T cell therapy without clear evidence of compromising efficacy; however, further investigations are necessary.
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