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:Current Frontline Treatment of Diffuse Large B-Cell Lymphoma.
Current Frontline Treatment of Diffuse Large B-Cell Lymphoma.
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弥漫大B细胞淋巴瘤(DLBCL)是非霍奇金淋巴瘤最常见的亚型,是一种侵袭性强且生物学异质性高的疾病。风险分层和治疗方案根据疾病分期、肿瘤负荷以及其他临床和生物学因素而有所不同,这些因素包括国际预后指数、细胞起源和其他分子亚型。利妥昔单抗(Rituxan)、环磷酰胺、多柔比星、长春新碱和泼尼松(R-CHOP)是目前的标准治疗,可治愈超过60%的患者。放疗的作用主要限于局限期疾病患者。在老年患者中,基于基线体能和功能状态的老年评估有助于在疗效与毒性之间取得平衡,从而优化治疗。尽管大量随机试验未能超越R-CHOP,但POLARIX试验(NCT03274492)最近的一份新闻稿提示,在利妥昔单抗、环磷酰胺、多柔比星和泼尼松中加入维泊妥珠单抗(Polivy)(pola-R-CHP)可改善无进展生存期,并可能在符合条件的患者中取代R-CHOP。正在进行的试验正在探索整合其他新型药物的前线治疗,包括各种小分子药物、双特异性抗体和CAR-T 细胞治疗,初步结果令人鼓舞。明确R-CHOP无效的高危疾病患者群体至关重要。通过细化分子亚型、定量PET指标(如代谢肿瘤体积)以及使用中期PET和循环肿瘤DNA分析进行动态风险评估来筛选患者,可能实现个体化的、基于应答调整的治疗策略,从而进一步改善DLBCL的预后。
Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin lymphoma, is an aggressive and biologically heterogeneous disease. Risk stratification and treatment algorithms vary based on stage of disease and bulk along with other clinical and biological factors, including the International Prognostic Index, cell of origin, and other molecular subsets. Rituximab (Rituxan), cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the current standard of care and cures more than 60% of patients. The role of radiotherapy is largely restricted to patients with limited-stage disease. In elderly patients, geriatric assessments of baseline fitness and functional status help optimize therapy based on the balance of efficacy and toxicity.
While numerous randomized trials have failed to improve upon R-CHOP, a recent press release from the POLARIX trial (NCT03274492) suggests that adding polatuzumab vedotin (Polivy) to rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP) improves progression-free survival and may replace R-CHOP in eligible patients. Ongoing trials are exploring frontline therapy that integrates other novel agents, including various small molecules, bispecific antibodies, and chimeric antigen receptor T-cell therapy, with promising preliminary results.
Defining a population of patients with high-risk disease in whom R-CHOP is not effective is critical. Patient selection based on refining molecular subsets, quantitative PET metrics such as metabolic tumor volume, and dynamic risk assessments using interim PET and circulating tumor DNA analysis may allow for a personalized, response-adapted approach that will further improve outcomes in DLBCL.
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