Sasse S, Momotow J, Engert A
Medizinische Klinik I, Uniklinik Köln, Kerpener Str. 62, 50937, Köln, Deutschland.
Deutsche Hodgkin Studiengruppe (GHSG), Uniklinik Köln, Kerpener Str. 62, 50937, Köln, Deutschland.
Internist (Berl). 2020 Jul;61(7):660-668. doi: 10.1007/s00108-020-00811-2.
Checkpoint blockade contributes to the immunosuppressive microenvironment in classical Hodgkin lymphoma (cHL) and in particular the interaction of Hodgkin cells and macrophages with T‑cells and natural killer cells via programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1).
The aim of this article is the evaluation the role and potential of checkpoint blockade in cHL as compared with the results of standard chemo- and radiotherapy.
We analyzed preclinical and clinical data from phase I and phase II studies with checkpoint blockade in cHL.
In 60-70% of patients with chemotherapy-refractory cHL, PD‑1 blockade results in responses. Overall survival is excellent and a small number of patients achieve persistent response. Thus, the use of anti-PD‑1 monoclonal antibodies has become an important treatment approach in relapsed cHL in line with the label. The results of first-line therapy are still preliminary; initial phase II studies using nivolumab in combination with doxorubicin (=adriamycin), vinblastin and dacarbazin (AVD) in early unfavorable or advanced stages showed response rates of up to 90%. Thus, implementing immunomodulatory approaches using PD 1‑blockade have resulted in a significant reduction of chemotherapy. This might represent a paradigm shift in the therapy of cHL.
检查点阻断促成了经典型霍奇金淋巴瘤(cHL)中的免疫抑制微环境,特别是霍奇金细胞和巨噬细胞通过程序性细胞死亡蛋白1(PD-1)和程序性细胞死亡蛋白1配体1(PD-L1)与T细胞和自然杀伤细胞之间的相互作用。
本文旨在评估与标准化疗和放疗结果相比,检查点阻断在cHL中的作用和潜力。
我们分析了cHL中使用检查点阻断的I期和II期研究的临床前和临床数据。
在60%-70%化疗难治性cHL患者中,PD-1阻断可产生反应。总生存率良好,少数患者可实现持续缓解。因此,按照药品说明书,使用抗PD-1单克隆抗体已成为复发cHL的一种重要治疗方法。一线治疗结果仍属初步;在早期高危或晚期阶段使用纳武单抗联合阿霉素、长春花碱和达卡巴嗪(AVD)的初始II期研究显示缓解率高达90%。因此,采用PD-1阻断的免疫调节方法已使化疗显著减少。这可能代表了cHL治疗的范式转变。