Yonezawa Hajime, Narita Yoshitaka, Nagane Motoo, Mishima Kazuhiko, Terui Yasuhito, Arakawa Yoshiki, Asai Katsunori, Fukuhara Noriko, Sugiyama Kazuhiko, Shinojima Naoki, Aoi Arata, Nishikawa Ryo
Department of Neurosurgery, Kagoshima University Hospital, Kagoshima, Kagoshima, Japan.
Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan.
Neurooncol Adv. 2024 Apr 22;6(1):vdae037. doi: 10.1093/noajnl/vdae037. eCollection 2024 Jan-Dec.
The ONO-4059-02 phase 1/2 study showed favorable efficacy and acceptable safety profile of tirabrutinib, a second-generation Bruton's tyrosine kinase inhibitor, for relapsed/refractory primary central nervous system lymphoma (PCNSL). Here, we report the long-term efficacy and safety after a 3-year follow-up.
Eligible patients were aged ≥ 20 years with histologically diagnosed PCNSL and KPS of ≥ 70. Patients received oral tirabrutinib once daily at 320 or 480 mg, or 480 mg under fasted conditions.
Between October 19, 2017, and June 13, 2019, 44 patients were enrolled: 33 and 9 had relapsed and refractory, respectively. The 320, 480, and 480 mg fasted groups included 20, 7, and 17 patients, respectively. The median follow-up was 37.1 months. The overall response rate was 63.6% (95% CI: 47.8-77.6) with complete response (CR), unconfirmed CR, and partial response in 9, 7, and 12 patients, respectively. The median duration of response (DOR) was 9.2 months, with a DOR rate of 19.8%; the median progression-free survival (PFS) and median overall survival (OS) were 2.9 months and not reached, respectively, with PFS and OS rates of 13.9% and 56.7%, respectively. Adverse events occurred in 38 patients (86.4%): grade ≥ 3 in 23 (52.3%) including 1 patient with grade 5 events. KPS and quality of life (QoL) scores were well maintained among patients receiving long-term treatment.
The results demonstrated the long-term clinical benefit of tirabrutinib, with deep and durable response in a subset of patients and acceptable safety profile, while KPS and QoL scores were maintained.
ONO-4059-02 1/2期研究显示，第二代布鲁顿酪氨酸激酶抑制剂替拉布替尼对复发/难治性原发性中枢神经系统淋巴瘤（PCNSL）具有良好的疗效和可接受的安全性。在此，我们报告3年随访后的长期疗效和安全性。
符合条件的患者年龄≥20岁，经组织学确诊为PCNSL，KPS≥70。患者每日口服一次替拉布替尼，剂量为320或480mg，或在禁食条件下服用480mg。
2017年10月19日至2019年6月13日，共纳入44例患者：其中33例复发，9例难治。320mg、480mg和480mg禁食组分别包括20例、7例和17例患者。中位随访时间为37.1个月。总缓解率为63.6%（95%CI：47.8-77.6），其中完全缓解（CR）、未确认CR和部分缓解分别为9例、7例和12例。中位缓解持续时间（DOR）为9.2个月，DOR率为19.8%；中位无进展生存期（PFS）和中位总生存期（OS）分别为2.9个月和未达到，PFS率和OS率分别为13.9%和56.7%。38例患者（86.4%）发生不良事件：23例（52.3%）为≥3级，其中1例为5级事件。接受长期治疗的患者KPS和生活质量（QoL）评分保持良好。
结果表明替拉布替尼具有长期临床获益，部分患者有深度且持久的缓解，安全性可接受，同时KPS和QoL评分得以维持。
