霍奇金淋巴瘤的免疫治疗:现状与未来策略

Immunotherapy in Hodgkin Lymphoma: Present Status and Future Strategies.

作者信息

Vassilakopoulos Theodoros P, Chatzidimitriou Chrysovalantou, Asimakopoulos John V, Arapaki Maria, Tzoras Evangelos, Angelopoulou Maria K, Konstantopoulos Kostas

机构信息

Department of Haematology and Bone Marrow Transplantation, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece.

出版信息

Cancers (Basel). 2019 Jul 29;11(8):1071. doi: 10.3390/cancers11081071.

Abstract

Although classical Hodgkin lymphoma (cHL) is usually curable, 20-30% of the patients experience treatment failure and most of them are typically treated with salvage chemotherapy and autologous stem cell transplantation (autoSCT). However, 45-55% of that subset further relapse or progress despite intensive treatment. At the advanced stage of the disease course, recently developed immunotherapeutic approaches have provided very promising results with prolonged remissions or disease stabilization in many patients. Brentuximab vedotin (BV) has been approved for patients with relapsed/refractory cHL (rr-cHL) who have failed autoSCT, as a consolidation after autoSCT in high-risk patients, as well as for patients who are ineligible for autoSCT or multiagent chemotherapy who have failed ≥ two treatment lines. However, except of the consolidation setting, 90-95% of the patients will progress and require further treatment. In this clinical setting, immune checkpoint inhibitors (CPIs) have produced impressive results. Both nivolumab and pembrolizumab have been approved for rr-cHL after autoSCT and BV failure, while pembrolizumab has also been licensed for transplant ineligible patients after BV failure. Other CPIs, sintilimab and tislelizumab, have been successfully tested in China, albeit in less heavily pretreated populations. Recent data suggest that the efficacy of CPIs may be augmented by hypomethylating agents, such as decitabine. As a result of their success in heavily pretreated disease, BV and CPIs are moving to earlier lines of treatment. BV was recently licensed by the FDA for the first-line treatment of stage III/IV Hodgkin lymphoma (HL) in combination with AVD (only stage IV according to the European Medicines Agency (EMA)). CPIs are currently being evaluated in combination with AVD in phase II trials of first-line treatment. The impact of BV and CPIs was also investigated in the setting of second-line salvage therapy. Finally, combinations of targeted therapies are under evaluation. Based on these exciting results, it appears reasonable to predict that an improvement in survival and a potential increase in the cure rates of cHL will soon become evident.

摘要

尽管经典型霍奇金淋巴瘤(cHL)通常可治愈,但20%至30%的患者会出现治疗失败,其中大多数患者通常接受挽救性化疗和自体干细胞移植(autoSCT)。然而,尽管进行了强化治疗,该亚组中有45%至55%的患者会进一步复发或病情进展。在疾病进程的晚期,最近开发的免疫治疗方法在许多患者中取得了非常有前景的结果,实现了长期缓解或病情稳定。贝林妥欧单抗(BV)已被批准用于自体干细胞移植失败的复发/难治性cHL(rr-cHL)患者、高危患者自体干细胞移植后的巩固治疗,以及不符合自体干细胞移植或多药化疗条件且≥二线治疗失败的患者。然而,除了巩固治疗外,90%至95%的患者病情会进展,需要进一步治疗。在这种临床情况下,免疫检查点抑制剂(CPls)取得了令人瞩目的结果。纳武单抗和帕博利珠单抗均已被批准用于自体干细胞移植和BV治疗失败后的rr-cHL,而帕博利珠单抗也已被批准用于BV治疗失败后不符合移植条件的患者。其他CPls,如信迪利单抗和替雷利珠单抗,已在中国成功进行了试验,尽管受试人群的预处理程度较低。最新数据表明,去甲基化药物(如地西他滨)可能会增强CPls的疗效。由于它们在预处理程度较高的疾病中取得了成功,BV和CPls正在转向更早期的治疗方案。BV最近获得美国食品药品监督管理局(FDA)批准,可与AVD联合用于III/IV期霍奇金淋巴瘤(HL)的一线治疗(欧洲药品管理局(EMA)仅批准用于IV期)。目前,CPls正在一线治疗的II期试验中与AVD联合进行评估。BV和CPls在二线挽救治疗中的影响也得到了研究。最后,靶向治疗的联合方案正在评估中。基于这些令人振奋的结果,有理由预测cHL的生存率将会提高,治愈率可能也会随之增加,且这一趋势将很快显现。

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