Ramadan Safaa, Radice Tommaso, Ismail Ahmed, Fiori Stefano, Tarella Corrado
Division of Onco-Hematology, European Institute of Oncology, IRCCS, Milan, Italy.
Department of Medical Oncology, NCI-Cairo University, Cairo, Egypt.
Expert Rev Hematol. 2022 Apr;15(4):295-304. doi: 10.1080/17474086.2022.2061455. Epub 2022 Apr 25.
Primary CNS lymphoma (PCNSL) has traditionally been treated with induction HD-MTX-based chemotherapy, followed by consolidation whole-brain radiotherapy. However, this approach is associated with significant neurocognitive complications, especially in older patients. Therefore, different consolidation protocols have been evaluated. High-dose chemotherapy followed by autologous stem cell transplantation (HD-ASCT) has the best long-term survival outcomes in younger patients.
In this review of the literature, we focus on the overall therapeutic strategy and advances in the management of the aggressive primary CNS B-cell lymphomas.
In young and fit PCNSL patients, HD-ASCT is the preferred consolidation strategy to achieve long-term survivals. Older patients with good performance status should also be evaluated for MTX-based induction polychemotherapy followed by ASCT. However, management of PCNSL patients remains challenging, and new avenues with targeted therapies are under investigation. To date, ibrutinib, lenalidomide, and immune checkpoint inhibitors appearto be promising in PCNSL. However, as monotherapy, durable responses are less likely to be achieved. Unfortunately, when combined with chemoimmunotherapy, considerable toxicity and mortality have been reported. Clinical trials on these molecules are aiming to reduce toxicity and maintain responses. CAR-T-cell therapy has recently emerged as a further option. It has shown efficacy in patients with secondary CNS lymphoma, with few but encouraging results in primary CNSL.
原发性中枢神经系统淋巴瘤（PCNSL）传统上采用以大剂量甲氨蝶呤（HD-MTX）为基础的诱导化疗，随后进行巩固性全脑放疗。然而，这种方法会引发显著的神经认知并发症，尤其是在老年患者中。因此，人们对不同的巩固方案进行了评估。大剂量化疗后进行自体干细胞移植（HD-ASCT）在年轻患者中具有最佳的长期生存结果。
在本次文献综述中，我们聚焦于侵袭性原发性中枢神经系统B细胞淋巴瘤的整体治疗策略及管理进展。
对于年轻且健康的PCNSL患者，HD-ASCT是实现长期生存的首选巩固策略。对于身体状况良好的老年患者，也应评估是否采用以MTX为基础的诱导联合化疗，随后进行ASCT。然而，PCNSL患者的管理仍然具有挑战性，靶向治疗的新途径正在研究中。迄今为止，伊布替尼、来那度胺和免疫检查点抑制剂在PCNSL中似乎很有前景。然而，作为单一疗法，不太可能实现持久缓解。不幸的是，当与化疗免疫疗法联合使用时，已报道有相当大的毒性和死亡率。关于这些分子的临床试验旨在降低毒性并维持疗效。嵌合抗原受体T细胞（CAR-T）疗法最近成为另一种选择。它在继发性中枢神经系统淋巴瘤患者中已显示出疗效，在原发性中枢神经系统淋巴瘤中虽结果不多但令人鼓舞。
