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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Case Report: Long-term survival of refractory high-grade B-cell lymphoma with MYC, BCL2, and BCL6 rearrangements through glofitamab monotherapy consolidated by ASCT.
Case Report: Long-term survival of refractory high-grade B-cell lymphoma with MYC, BCL2, and BCL6 rearrangements through glofitamab monotherapy consolidated by ASCT.
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早期复发或原发难治的高级别B细胞淋巴瘤(HGBCL)患者预后始终较差。即使强化化疗或CAR-T 细胞治疗也并不总是最佳解决方案。本文报道一例伴有MYC、BCL2和BCL6重排的难治性高级别B细胞淋巴瘤(三打击HGBCL)患者,在接受六个周期的glofitamab单药诱导治疗后,序贯自体干细胞移植(ASCT)巩固治疗,实现了完全代谢缓解(CMR)。该患者已获得持续CMR,自疾病进展以来的无进展生存期(PFS)为25个月(仍在持续)。在ASCT期间、干细胞植入前发生乙型肝炎病毒(HBV)血清学转换,经恩替卡韦有效抑制。
我们通过流式细胞术监测了该病例的免疫功能。观察到T细胞上PD-1表达下调以及调节性T细胞(Tregs)比例降低,与免疫功能充分激活一致,这可能解释了该患者为何能快速应答并维持持久疗效。免疫分析还显示B细胞亚群耗竭以及初始/记忆T细胞比例紊乱,提示免疫衰老表型。推测双特异性抗体治疗后免疫功能的过度激活促进了免疫衰老,这一点需要引起关注。本病例凸显了glofitamab诱导治疗后序贯ASCT巩固治疗在侵袭性三打击HGBCL中实现持久缓解的潜力。双特异性抗体治疗后的免疫功能应予以监测,并需要进一步研究。
Patients with high-grade B-cell lymphoma (HGBCL), who are in early relapse or primary refractory, always have poor outcomes. Even intensive chemotherapy or CAR-T cell therapy is not always the best solution.
Here is a case of refractory high-grade B-cell lymphoma with MYC, BCL2, and BCL6 rearrangements (triple-hit HGBCL), who achieved complete metabolic remission (CMR) following six cycles of glofitamab monotherapy induction and followed by autologous stem cell transplantation (ASCT) consolidation. The patient has achieved a sustained CMR and a progression-free survival (PFS) of 25 months (ongoing) from progression. Hepatitis B virus (HBV) seroconversion occurred during ASCT before stem cell engraftment, and was effectively suppressed with entecavir. Immune function was monitored in our case by flow cytometry.
Downregulation of PD-1 expression on T cells and a reduced proportion of regulatory T cells (Tregs) were observed, consistent with fully activated immune function, which may explain why the patient responded rapidly and maintained durable efficacy. Immune analysis also exhibited B cell subset exhaustion and a disrupted na ve/memory T cell ratio which suggested an immunosenescence phenotype.
It is speculated that an over activation of immune function promotes immunosenescence following bispecific antibody therapy, this needs attention. This case highlights the potential of glofitamab induction followed by ASCT consolidation to achieve durable remission in aggressive triple-hit HGBCL. The immune function after bispecific antibody treatment should be monitored and needs further investigation.
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