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:Diffuse large B-cell lymphoma.
Diffuse large B-cell lymphoma.
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大B细胞淋巴瘤是侵袭性非霍奇金淋巴瘤的原型,既是最常见的淋巴瘤,也在全球淋巴瘤相关死亡负担中占最高比例。近40年来,治疗目标一直是“治愈”,最初基于CHOP(环磷酰胺、多柔比星、长春新碱、泼尼松),随后为利妥昔单抗联合CHOP。
然而,该病在临床、病理和生物学上具有显著异质性,并非所有患者都能治愈。遗憾的是,理解这种生物学异质性并将其纳入治疗决策尚未成为标准治疗。尽管存在这一差距,我们如今在一线、复发/难治性治疗方面已取得显著进展。POLARIX试验首次表明,在前瞻性随机3期研究中,无进展生存期得到改善。在复发/难治性治疗方面,目前已有许多获批药物/方案,且多种双特异性抗体即将加入可选武器库。虽然CAR-T 细胞治疗在其他地方有详细讨论,但它已迅速成为二线及以后治疗中的极佳选择。遗憾的是,老年人群等特殊人群的结局仍然较差,且在试验中代表性不足,尽管新一代试验旨在解决这一差异。这篇简要综述将重点介绍关键问题和进展,这些进展为越来越多患者带来了更好的结局。
Large B-cell lymphoma, the prototype of aggressive non-Hodgkin lymphomas, is both the most common lymphoma and accounts for the highest global burden of lymphoma-related deaths. For nearly 4 decades, the goal of treatment has been "cure", first based on CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), and subsequently with rituximab plus CHOP.
However, there is significant clinical, pathologic, and biologic heterogeneity, and not all patients are cured. Understanding and incorporating this biologic heterogeneity into treatment decisions unfortunately is not yet standard of care. Despite this gap, we now have significant advances in frontline, relapsed, and refractory settings. The POLARIX trial shows, for the first time, improved progression-free survival in a prospective randomized phase 3 setting. In the relapsed and refractory settings, there are now many approved agents/regimens, and several bispecific antibodies poised to join the arsenal of options.
While chimeric antigen receptor T-cell therapy is discussed in detail elsewhere, it has quickly become an excellent option in the second-line setting and beyond. Unfortunately, special populations such as older adults continue to have poor outcomes and be underrepresented in trials, although a new generation of trials aim to address this disparity. This brief review will highlight the key issues and advances that offer improved outcomes to an increasing portion of patients.
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