滤泡淋巴瘤的分子靶向及免疫治疗新进展

Progress in molecular targeted therapy and immunotherapy for follicular lymphoma

滤泡淋巴瘤(follicular lymphoma,FL)为最常见的惰性非霍奇金淋巴瘤(non-Hodgkin lymphoma,NHL),其5年生存率较高,但多数患者最终会发展成为复发/难治性淋巴瘤。其特点为进展缓慢,且晚期较难治愈。因此,治疗策略目标为高疗效及低毒性。基于各种新型药物的不断出现,FL患者的预后得到改善。目前的临床研究结果中,具有良好活性的分子靶向药物包括BTK抑制剂、PI3K抑制剂、Bcl-2抑制剂、EZH2抑制剂等。此外,免疫调节药物,如来那度胺、GA101、CAR-T、PD-1、抗体-药物结合物以及双特异性抗体等均显示出较好的治疗效果,为改善FL患者的预后提供新的可能。免疫治疗需考虑药物不良反应,以选择合适方式减轻毒性。本文就FL免疫治疗及分子靶向治疗的新进展进行综述。

Follicular lymphoma(FL),the most common indolent non-Hodgkin lymphoma(NHL),has a high five-year survival rate.However,it will eventually develop into relapsed/refractory lymphoma in a subset of patients.FL is characterized by slow growth and is often considered incurable in advanced stages.Therefore,treatment strategies should be aimed at attaining higher efficacy while minimizing toxicity.A number of novel,nonchemotherapeutic agents have been developed for FL and the prognosis of patients with FL is improving.Currently,clinical trials on targeted molecular drugs with good activity including BTK inhibitors,PI3K inhibitors,Bcl-2 inhibitors,EZH2 inhibitors,etc.In addition,immunotherapy drugs,such as lenalidomide,obinutuzumab,chimeric antigen receptor T-cell(CAR-T)immunotherapy,programmed cell death-1(PD-1)antibody-drug conjugates,and bispecific antibodies,have shown good therapeutic efficacy,thereby providing new possibilities for improving the prognosis of patients with FL.Utilization of various forms of immunotherapies requires careful consideration of the unique toxicities associated with these therapies and the means to mitigate them.This article reviews the above-mentioned new developments in immunotherapies and targeted molecular therapies for FL.