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:Treatment strategies for patients with diffuse large B-cell lymphoma.
Treatment strategies for patients with diffuse large B-cell lymphoma.
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弥漫大B细胞淋巴瘤(DLBCL)如今已成为一种可治愈的疾病,一线治疗为R-CHOP,但仍有30-40%的患者无应答或此后复发。近年来,若干即将出现的新选择正在改善复发/难治性(R/R)DLBCL的治疗格局,首先是抗CD19CAR-T 细胞,其已作为三线治疗的标准治疗,并正迅速向R-CHOP后难治或早期复发患者的二线治疗推进。在这些新疗法中,最为相关的是polatuzumab联合利妥昔单抗和苯达莫司汀、tafasitamab联合来那度胺用于不适合移植的患者,以及CD3xCD20双特异性抗体,但还有若干其他药物和策略正在研发中。另一方面,在过去20年中,为改善DLBCL一线治疗优于R-CHOP的结局,人们进行了诸多努力,包括缩短周期间隔、强化治疗或在R-CHOP基础上加用新药,但迄今均未成功。近期将抗CD79b抗体药物偶联物polatuzumab vedotin联合R-CHP以及抗BCL2药物venetoclax联合R-CHOP的研究显示出有前景的结果。基于DLBCL不同分子亚型的个体化治疗这一即将出现的新策略的初步数据令人鼓舞,显示出优于标准R-CHOP的获益。在本文中,将批判性综述有关DLBCL一线及R/R治疗中现有及即将出现的新疗法格局的文献数据。
Diffuse large B-cell lymphoma (DLBCL) is nowadays a curable disease with the frontline treatment R-CHOP, but 30-40% of patients are still unresponsive or relapse thereafter. In the recent era several upcoming new options are improving the therapeutic landscape for relapsed/refractory (R/R) DLBCL setting, first of all anti-CD19 chimeric antigen receptor T-cells (CAR-T) that already represent a standard of care as third-line therapy and are rapidly moving as second-line treatment for those who are refractory or early relapse after R-CHOP. Among these new therapies, the combinations polatuzumab plus rituximab and bendamustine, tafasitamab plus lenalidomide for transplant ineligible patients, and CD3xCD20 bispecific antibodies are the most relevant, but several other agents and strategies are on the way.
On the other hand, in the last 20 years, several efforts have been spent in the attempt to ameliorate the outcome over R-CHOP for the frontline treatment of DLBCL shortening the interval between the cycles or intensifying treatment or adding novel drugs to R-CHOP without success, so far. Recent studies combining the anti-CD79b antibody-drug conjugate polatuzumab vedotin plus R-CHP and the anti-BCL2 agent venetoclax plus R-CHOP showed promising results.
Preliminary data of new upcoming strategies characterized by a tailored therapy based on different molecular subtypes of DLBCL are encouraging, showing a benefit over the standard R-CHOP. In this manuscript, the literature data on the landscape of new therapies available and upcoming for both frontline and R/R settings of DLBCL will be critically reviewed.
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