文章：

淋巴瘤联合疗法中临床PD-1/PD-L1阻断剂的应用研究

Clinical PD-1/PD-L1 Blockades in Combination Therapies for Lymphomas

原文发布日期：14 November 2023

DOI: 10.3390/cancers15225399

类型: Article

开放获取: 是

英文摘要：

Immunotherapy with the programmed cell death protein 1 (PD-1)/PD-1 ligand (PD-L1) blockade has revolutionized the treatment of advanced solid cancers. However, these clinical benefits have been limited to cases of malignant lymphomas, showing promising results for only classic Hodgkin lymphoma (cHL) and primary mediastinal B-cell lymphoma (PMBCL). To bring clinical benefits to more patients with lymphoma, numerous combination therapies involving PD-1/PD-L1 blockade have been tested in clinical trials in both frontline and relapsed/refractory settings. This article reviews the current landscape of combination therapies with PD-1/PD-L1 blockade for lymphoma and discusses the potential therapeutic approaches. An interim analysis of a phase 3 study demonstrated increased progression-free survival with nivolumab combination therapy over the current frontline treatment in patients with advanced-stage cHL. The results of combination therapies for aggressive B-cell lymphomas, except for PMBCL, have been disappointing. Several clinical trials of combined PD-1/PD-L1 blockade and Bruton’s tyrosine kinase inhibitors are exploring its efficacy in patients with chronic lymphocytic leukemia (CLL) with Richter transformation. Several T-cell lymphoma subtypes respond to PD-1/PD-L1 blockade monotherapy. Further clinical trials are underway to investigate appropriate combination regimens with PD-1/PD-L1 blockade, especially for cHL, CLL with Richter transformation, and T-cell lymphoma, in both frontline and relapsed/refractory settings.

摘要翻译： 

程序性细胞死亡蛋白1（PD-1）/PD-1配体（PD-L1）阻断疗法已彻底改变了晚期实体癌的治疗格局。然而，该疗法的临床获益目前主要局限于恶性淋巴瘤领域，仅在经典霍奇金淋巴瘤（cHL）和原发性纵隔B细胞淋巴瘤（PMBCL）中展现出显著疗效。为扩大淋巴瘤患者的临床获益范围，多项包含PD-1/PD-L1阻断的联合疗法已在初治及复发/难治性淋巴瘤的临床试验中开展评估。本文系统综述了PD-1/PD-L1阻断联合疗法在淋巴瘤领域的当前进展，并探讨了潜在的治疗策略。一项三期临床试验的中期分析显示，在晚期cHL患者中，纳武利尤单抗联合疗法相较于现行一线治疗方案显著延长了无进展生存期。除PMBCL外，侵袭性B细胞淋巴瘤的联合疗法结果尚不理想。多项PD-1/PD-L1阻断联合布鲁顿酪氨酸激酶抑制剂的临床试验正在探索其对伴有Richter转化的慢性淋巴细胞白血病（CLL）患者的疗效。部分T细胞淋巴瘤亚型对PD-1/PD-L1阻断单药治疗具有应答。针对cHL、伴有Richter转化的CLL及T细胞淋巴瘤，目前正在开展更多临床试验以探索PD-1/PD-L1阻断在初治及复发/难治场景下的最佳联合治疗方案。

原文链接：

Clinical PD-1/PD-L1 Blockades in Combination Therapies for Lymphomas