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:Current treatment algorithm: diffuse large B cell lymphoma.
弥漫性大B细胞淋巴瘤(DLBCL)是一种侵袭性B细胞恶性肿瘤,也是最常见的淋巴瘤亚型。
弥漫性大B细胞淋巴瘤(DLBCL)是一种侵袭性B细胞恶性肿瘤,也是最常见的淋巴瘤亚型。治疗以治愈为目的,预计约三分之二的患者可获得持久的长期生存。为实现这一目标,通常将基于蒽环类药物的化疗联合利妥昔单抗作为初始治疗。治疗方案根据疾病分期、预后临床特征以及组织学或分子亚型分类进行优化。在DLBCL活化B细胞亚型患者中,联合方案中通常包含polatuzumab vedotin。对于存在Myc和BCL-2重排的患者,采用治疗强度更高的方案。尽管采用了这种风险适应策略,仍有至少三分之一的患者复发。对于在1年内复发或对初始治疗耐药的患者,通常接受嵌合抗原受体(CAR)T细胞治疗。对于在初始治疗后超过1年复发的患者,则给予挽救性化疗序贯自体干细胞移植。对于不适合细胞治疗的患者,或在CAR T细胞治疗后进展的患者,治疗为姑息性,包括给予双特异性抗体或抗体药物偶联物联合方案。为进一步改善DLBCL患者的结局,目前正在测试将细胞治疗和双特异性治疗纳入一线治疗。
Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell malignancy and is the most common subtype of lymphoma. Treatment is administered with curative intent and approximately two thirds of patients are expected to have durable long-term survival. To achieve this, anthracycline-based chemotherapy in combination with rituximab is typically administered as initial therapy. Management is optimized based on the disease stage, prognostic clinical features, and histological or molecular subclassification. In patients with the activated B-cell subtype of DLBCL, polatuzumab vedotin is commonly included in the combination. For those with Myc and BCL-2 rearrangements, a more treatment intense approach is used. Despite this risk-adapted approach, at least one third of patients relapse. Those who relapse within 1 year, or are resistant to initial therapy typically receive chimeric antigen receptor (CAR) T-cell therapy. For those relapsing more than a year post initial treatment, salvage chemotherapy followed by an autologous stem cell transplant is offered. In patients ineligible for cellular therapy, or those who progress after CAR T-cell treatment, management is palliative and includes administration of bispecific antibodies or antibody drug conjugate combinations. To further improve the outcome of DLBCL patients, incorporation of cellular and bispecific therapies into front-line treatment is currently being tested.
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