决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:SOHO State of the Art Updates and Next Questions | Diffuse Large B-Cell Lymphoma in Older Adults: A Comprehensive Review.
SOHO State of the Art Updates and Next Questions | Diffuse Large B-Cell Lymphoma in Older Adults: A Comprehensive Review.
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在复发/难治性(R/R)情况下,抗 CD19 CAR-T 细胞治疗(CAR-T)现已成为原发性难治性疾病或完成治疗后 12 个月内复发患者的标准治疗。
弥漫性大B细胞淋巴瘤(DLBCL)老年患者(OA)群体具有异质性,治疗结局不理想。本综述识别并讨论老年DLBCL患者照护中的独特挑战,阐述当前老年综合评估(GA)工具的作用和局限,以及如何将患者体能状况纳入治疗决策。我们提出在常规临床实践和临床试验中实施GA的最佳做法。应用最广泛的工具是简化GA(sGA),可将患者分为适合、不适合和衰弱三类。适合治疗的患者可从足剂量/以治愈为目标的方案中获益;对不适合治疗者,应考虑降低化疗强度。衰弱的DLBCL患者是重大未满足需求,目前缺乏令人满意的治疗选择。研究者正在探索将新型疗法纳入无化疗方案,早期结果令人鼓舞。复发/难治性(R/R)场景中,抗CD19 CAR-T 细胞疗法(CAR-T)现已成为原发难治或治疗结束后12个月内复发患者的标准治疗。治疗结束超过12个月后复发且体能适合的老年患者,仍可考虑自体干细胞移植。双特异性抗体近期获批是一项重要进展,可使不适合CAR-T 的老年患者显著获益。其他可用于不适合CAR-T 或CAR-T 后疾病进展患者的方案包括泊洛妥珠单抗-利妥昔单抗-苯达莫司汀、tafasitamab-来那度胺、loncastuximab,或利妥昔单抗-吉西他滨-奥沙利铂等化疗方案。我们讨论R/R DLBCL治疗模式的变化,并重点介绍近期学术会议上的新数据,这些数据有望改善这一脆弱患者群体的结局。
Older adults (OA) with DLBCL are a heterogenous population with suboptimal outcomes. In this review, we identify and address the unique challenges encountered in the care of OA with DLBCL. We elaborate on the role and limitations of current geriatric assessment (GA) tools and ways to incorporate fitness in therapeutic decision making. We suggest best practices to implement GA in routine practice and clinical trials. The most widely used tool is simplified GA (sGA) which categorizes patients into fit, unfit and frail groups. Patients who are fit benefit from full dose/curative approach, whereas consideration should be made to reduce the intensity of chemotherapy for unfit patients. Frail patients with DLBCL are a major unmet need without any satisfactory treatment options. Ongoing investigations combining novel therapies into chemotherapy-free regimens are underway with promising early results. In the relapsed/refractory (R/R) setting, anti-CD19 CAR-T cell therapy (CART) is now the standard of care for primary refractory disease or relapse within 12 months of completing therapy. Autologous stem cell transplant is still a consideration for fit OA with relapse >12 months after completing therapy. The recent approval of bispecific antibodies is a welcome advance that will greatly benefit OA not eligible for CART. Other regimens available for patients ineligible for CART or for those who experience progression post-CART include polatuzumab-rituximab bendamustine, tafasitamab-lenalidomide, loncastuximab or chemotherapy-based approaches such as rituximab-gemcitabine-oxaliplatin. We discuss the changing paradigm in R/R DLBCL and spotlight emerging data from recent congresses that can improve outcomes in this vulnerable population.
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