Classical Hodgkin Lymphoma (cHL) is a highly curable disease, but around 20% of patients experience progression or relapse after standard frontline chemotherapy regimens. Salvage regimens followed by autologous stem cell transplants represent the historical treatment approach for these cases. In the last decade, with the increasing understanding of cHL biology and tumor microenvironment role in disease course, novel molecules have been introduced in clinical practice, improving outcomes in the relapsed/refractory setting. The anti-CD30 antibody-drug conjugated brentuximab vedotin and PD-1/PD-L1 checkpoint inhibitors represent nowadays curative options for chemorefractory patients, and randomized trials recently demonstrated their efficacy in frontline immune-chemo-combined modalities. Several drugs able to modulate the patients’ T-lymphocytes and NK cell activity are under development, as well as many anti-CD30 chimeric antigen receptor T-cell products. Multiple tumor aberrant epigenetic mechanisms are being investigated as targets for antineoplastic compounds such as histone deacetylase inhibitors and hypomethylating agents. Moreover, JAK2 inhibition combined with anti-PD1 blockade revealed a potential complementary therapeutic pathway in cHL. In this review, we will summarize recent findings on cHL biology and novel treatment options clinically available, as well as promising future perspectives in the field.
经典霍奇金淋巴瘤是一种高度可治愈的疾病，但约20%的患者在接受标准一线化疗方案后仍会出现疾病进展或复发。挽救性治疗方案联合自体干细胞移植历来是此类病例的标准治疗策略。近十年来，随着对经典霍奇金淋巴瘤生物学特性及肿瘤微环境在疾病进程中作用的深入理解，新型分子药物已应用于临床实践，显著改善了复发/难治性患者的治疗结局。抗CD30抗体药物偶联物维布妥昔单抗与PD-1/PD-L1检查点抑制剂现已成为化疗难治性患者的根治性选择，近期随机试验亦证实了其在联合免疫化疗一线治疗方案中的疗效。目前有多款能够调节患者T淋巴细胞和NK细胞活性的药物正处于研发阶段，同时多种抗CD30嵌合抗原受体T细胞产品也在开发中。组蛋白去乙酰化酶抑制剂和去甲基化药物等靶向肿瘤异常表观遗传机制的抗肿瘤化合物正在积极研究中。此外，JAK2抑制剂联合抗PD1阻断疗法在经典霍奇金淋巴瘤治疗中展现出潜在的协同治疗路径。本综述将系统阐述经典霍奇金淋巴瘤生物学机制的最新发现、临床可及的新型治疗方案，以及该领域未来具有前景的发展方向。
Advances in Hodgkin Lymphoma Treatment: From Molecular Biology to Clinical Practice
肿瘤(癌症)患者之家