Jaradat Jaber H, Alkhawaldeh Ibraheem M, Al-Bojoq Yousef, Ramadan Monther N, Abuawwad Mohammad T, Alabdallat Yasmeen Jamal, Nashwan Abdulqadir J
Faculty of Medicine, Mutah University, Al-Karak, Jordan.
Department of clinical medicine, Kasr Alainy School of Medicine, Cairo, Egypt.
Crit Rev Oncol Hematol. 2025 Feb;206:104597. doi: 10.1016/j.critrevonc.2024.104597. Epub 2024 Dec 15.
Primary central nervous system lymphoma (CNSL) is a rare, aggressive non-Hodgkin lymphoma confined to the CNS. Although radiation and chemotherapy, particularly high-dose methotrexate (HD-MTX), are effective treatments, the relapse rates remain high, prompting the exploration of novel therapeutic options. Ibrutinib, an irreversible Bruton tyrosine kinase (BTK) inhibitor, has shown promise in various B-cell malignancies, including CNSL.
This systematic review and meta-analysis aimed to evaluate the safety and efficacy of ibrutinib in the treatment of CNSL, focusing on overall response (OR), complete response (CR), partial response (PR), progression-free survival (PFS), overall survival (OS), and adverse events.
A comprehensive search of the PubMed, Google Scholar, and Scopus databases was conducted. The included studies were prospective and retrospective studies focusing on ibrutinib as monotherapy or in combination with CNSL. Data extraction and quality assessment were independently performed by two reviewers, and statistical analyses were conducted using R version 4.4.0.
Fourteen studies (eight cohort studies and six clinical trials) involving 784 patients were included. The median age was 61 years, with nearly equal sex distribution. The meta-analysis for CNSL, the partial response rate was 29.52 %, complete response rate was 49.19 %, and overall response rate was 72.11 %. For PCNSL, the partial response rate was 20.85 %, complete response rate was 48.13 %, and overall response rate was 66.92 %. For SCNSL, the partial response rate was 29.42 %, complete response rate was 44.64 %, and overall response rate was 66.82 %. Significant heterogeneity was observed in some comparisons. There were no significant differences in the efficacy of ibrutinib between CNSL subtypes.
Ibrutinib shows promising efficacy in improving partial and complete response rates in CNSL. The substantial heterogeneity observed underscores the need for further well-designed studies to confirm these findings and explore the optimal use of ibrutinib in CNSL treatment protocols. Future trials should consider comparing ibrutinib to standard therapies and investigate its long-term efficacy and safety profile.
原发性中枢神经系统淋巴瘤（CNSL）是一种罕见的、侵袭性非霍奇金淋巴瘤，局限于中枢神经系统。尽管放疗和化疗，尤其是大剂量甲氨蝶呤（HD - MTX）是有效的治疗方法，但复发率仍然很高，这促使人们探索新的治疗选择。依鲁替尼是一种不可逆的布鲁顿酪氨酸激酶（BTK）抑制剂，已在包括CNSL在内的各种B细胞恶性肿瘤中显示出前景。
本系统评价和荟萃分析旨在评估依鲁替尼治疗CNSL的安全性和有效性，重点关注总缓解率（OR）、完全缓解率（CR）、部分缓解率（PR）、无进展生存期（PFS）、总生存期（OS）和不良事件。
对PubMed、谷歌学术和Scopus数据库进行了全面检索。纳入的研究为前瞻性和回顾性研究，重点是依鲁替尼单药治疗或与CNSL联合治疗。由两名 reviewers 独立进行数据提取和质量评估，并使用R版本4.4.0进行统计分析。
纳入了14项研究（8项队列研究和6项临床试验），涉及784例患者。中位年龄为61岁，性别分布几乎相等。对CNSL的荟萃分析，部分缓解率为29.52%，完全缓解率为49.19%，总缓解率为72.11%。对于原发性中枢神经系统淋巴瘤（PCNSL），部分缓解率为20.85%，完全缓解率为48.13%，总缓解率为66.92%。对于继发性中枢神经系统淋巴瘤（SCNSL），部分缓解率为29.42%，完全缓解率为44.64%，总缓解率为66.82%。在一些比较中观察到显著的异质性。依鲁替尼在CNSL亚型之间的疗效没有显著差异。
依鲁替尼在提高CNSL的部分缓解率和完全缓解率方面显示出有前景的疗效。观察到的显著异质性强调需要进一步设计良好的研究来证实这些发现，并探索依鲁替尼在CNSL治疗方案中的最佳使用方法。未来的试验应考虑将依鲁替尼与标准疗法进行比较，并研究其长期疗效和安全性。
