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用于霍奇金淋巴瘤和非霍奇金淋巴瘤的检查点抑制剂及其他免疫疗法。

Checkpoint Inhibitors and Other Immune Therapies for Hodgkin and Non-Hodgkin Lymphoma.

作者信息

Matsuki Eri, Younes Anas

机构信息

Lymphoma Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 330, New York, NY, 10065, USA.

出版信息

Curr Treat Options Oncol. 2016 Jun;17(6):31. doi: 10.1007/s11864-016-0401-9.

Abstract

Treatment for relapsed/refractory (R/R) Hodgkin and non-Hodgkin lymphoma remains challenging. The introduction of rituximab to B cell non-Hodgkin lymphoma (B-NHL) treatment significantly improved patients' response rate and survival; however, approximately one third of patients with diffuse large B cell lymphoma, the most common B-NHL subtype, still have a relapse or become refractory after first-line therapy. More recently, antibody therapies and small-molecule inhibitors were approved for treating R/R lymphomas; these agents include brentuximab vedotin, ibrutinib, and idelalisib. Immune checkpoint inhibitors and other immune therapies are emerging treatments currently being evaluated in various clinical trials for their efficacy against lymphoid malignancies. Striking results from these treatment modalities have been observed in solid tumors, and evidence is accumulating to support their use in various lymphomas. The most exciting results from immune checkpoint inhibitor therapy have been seen in patients with R/R Hodgkin lymphoma, in whom the overall response rate has reached 60-80 %. Results in NHL are more similar to those seen in other solid malignancies, ranging between 20 and 40 %, depending on the histology. Formal approval of these drugs is being awaited, as are the results of combination therapy with checkpoint inhibitors and other treatment modalities, including conventional chemotherapy, small-molecule inhibitors, and other immune therapies. Although response rates have been promising, attention must be paid to the management of unique immune-related adverse events, which warrant close monitoring in some cases. Identification of biomarkers that predict response or severe adverse events using either the tumor specimen or peripheral blood would aid in selecting patients suited for these types of treatment as well as determining the ideal sequence of treatment within the realm of immune therapies.

摘要

复发/难治性(R/R)霍奇金淋巴瘤和非霍奇金淋巴瘤的治疗仍然具有挑战性。利妥昔单抗引入B细胞非霍奇金淋巴瘤(B-NHL)治疗后,显著提高了患者的缓解率和生存率;然而,弥漫性大B细胞淋巴瘤是最常见的B-NHL亚型,约三分之一的患者在一线治疗后仍会复发或产生耐药。最近,抗体疗法和小分子抑制剂被批准用于治疗R/R淋巴瘤;这些药物包括本妥昔单抗、伊布替尼和艾代拉里斯。免疫检查点抑制剂和其他免疫疗法是目前正在各种临床试验中评估其对淋巴恶性肿瘤疗效的新兴治疗方法。在实体瘤中已观察到这些治疗方式取得了显著效果,并且越来越多的证据支持它们在各种淋巴瘤中的应用。免疫检查点抑制剂疗法最令人兴奋的结果出现在R/R霍奇金淋巴瘤患者中,其总缓解率达到了60%-80%。在非霍奇金淋巴瘤中的结果与其他实体恶性肿瘤更为相似,根据组织学不同,缓解率在20%至40%之间。这些药物的正式批准正在等待中,免疫检查点抑制剂与其他治疗方式(包括传统化疗、小分子抑制剂和其他免疫疗法)联合治疗的结果也在等待中。尽管缓解率很有前景,但必须注意独特的免疫相关不良事件的管理,在某些情况下需要密切监测。利用肿瘤标本或外周血识别预测缓解或严重不良事件的生物标志物,将有助于选择适合这类治疗的患者,并确定免疫疗法领域内理想的治疗顺序。

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