淋巴瘤联合治疗中的临床PD-1/PD-L1阻断疗法

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

作者信息

Katsuya Hiroo, Suzumiya Junji, Kimura Shinya

机构信息

Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan.

Department of Hematology, Koga Community Hospital, Yaizu 425-0088, Japan.

出版信息

Cancers (Basel). 2023 Nov 14;15(22):5399. doi: 10.3390/cancers15225399.

Abstract

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

程序性细胞死亡蛋白1(PD-1)/PD-1配体(PD-L1)阻断免疫疗法彻底改变了晚期实体癌的治疗方式。然而,这些临床益处仅限于恶性淋巴瘤病例,仅对经典霍奇金淋巴瘤(cHL)和原发性纵隔B细胞淋巴瘤(PMBCL)显示出有前景的结果。为了给更多淋巴瘤患者带来临床益处,在一线和复发/难治性治疗环境的临床试验中测试了多种涉及PD-1/PD-L1阻断的联合疗法。本文综述了用于淋巴瘤的PD-1/PD-L1阻断联合疗法的当前情况,并讨论了潜在的治疗方法。一项3期研究的中期分析表明,对于晚期cHL患者,纳武单抗联合疗法比当前一线治疗的无进展生存期有所延长。除PMBCL外,侵袭性B细胞淋巴瘤联合疗法的结果令人失望。几项PD-1/PD-L1阻断与布鲁顿酪氨酸激酶抑制剂联合的临床试验正在探索其对Richter转化的慢性淋巴细胞白血病(CLL)患者的疗效。几种T细胞淋巴瘤亚型对PD-1/PD-L1阻断单药治疗有反应。正在进行进一步的临床试验,以研究在一线和复发/难治性治疗环境中与PD-1/PD-L1阻断联合的合适方案,特别是对于cHL、Richter转化的CLL和T细胞淋巴瘤。

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