原发性中枢神经系统淋巴瘤 (PCNSL) 是一种侵袭性淋巴瘤，可累及大脑、脊髓、软脑膜和眼睛。 PCNSL 预后仍然较差，5 年生存率为 30-40%。对于复发/难治性 (r/r) PCNSL 的治疗选择尤其有限。近年来，研究揭示了 PCNSL 的发病机制和致癌途径，从而促进了新疗法的发展。在这篇综述中，我们讨论了支持这些新药的证据，并介绍了正在进行的临床研究。 PCNSL 的关键致癌驱动因素包括 NFkB 通路的激活、细胞周期失调、体细胞超突变和免疫逃避，从而导致了针对靶向治疗和免疫治疗的研究抑制这些途径。此类方法包括 BTK 抑制剂、mTOR/PI3K 抑制剂、免疫调节剂 (IMID)、免疫检查点抑制剂和基于 CD19 的 CAR T 细胞。 PCNSL 的治疗方案正在迅速发展，未来可能会采用包括强化化疗方案和新疗法在内的多模式方法。© 2024。作者获得 Springer Science Business Media, LLC 的独家许可，施普林格自然的一部分。

Primary Central Nervous System Lymphoma (PCNSL) is an aggressive form of lymphoma that can involve the brain, spinal cord, leptomeninges and eyes. PCNSL prognosis continues to be poor, with 5-year survival rates of 30-40%. Therapeutic options are especially limited for relapsed/refractory (r/r) PCNSL. In recent years, studies shed light on the pathogenesis and oncogenic pathways driving PCNSL, leading to the development of novel therapeutics. In this review, we discuss the evidence supporting these novel agents and present ongoing clinical studies.Key oncogenic drivers of PCNSL include activation of the NFkB pathway, cell cycle dysregulation, somatic hypermutation and immune evasion, leading to the investigation of targeted therapeutics and immunotherapeutics to inhibit these pathways. Such approaches include BTK inhibitors, mTOR/PI3K inhibitors, immunomodulatory agents (IMIDs), immune checkpoint inhibitors and CD19-based CAR T-cells. The therapeutic repertoire for PCNSL is rapidly evolving, and a multi-modality approach including intensive chemotherapy regimens and novel therapies will likely be utilized in the future.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.