PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
■ONO-4059-021/2期研究显示了替拉鲁替尼的良好疗效和可接受的安全性，第二代布鲁顿酪氨酸激酶抑制剂，复发/难治性原发性中枢神经系统淋巴瘤（PCNSL）。这里,我们报告了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，组织学诊断为PCNSL和KPS≥70。患者接受每日一次口服tirabrutinib，剂量为320或480mg，或480毫克在禁食条件下。
■在2017年10月19日至2019年6月13日之间，纳入了44例患者：33例和9例复发和难治性，分别。320、480和480mg禁食组包括20、7和17名患者，分别。中位随访时间为37.1个月。总有效率为63.6%（95%CI：47.8-77.6），完全缓解（CR）。未经确认的CR，9、7和12名患者有部分反应，分别。中位反应持续时间（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)为2.9个月,分别,PFS和OS率为13.9%和56.7%，分别。不良事件发生在38例（86.4%）：23例（52.3%）中≥3级，包括1例5级事件。在接受长期治疗的患者中，KPS和生活质量（QoL）评分保持得很好。
■结果证明了替拉鲁替尼的长期临床益处，在部分患者中具有深度和持久的反应以及可接受的安全性，而KPS和QoL评分保持不变。
■符合条件的患者年龄≥20岁，组织学诊断为PCNSL和KPS≥70。患者接受每日一次口服tirabrutinib，剂量为320或480mg，或480毫克在禁食条件下。
■在2017年10月19日至2019年6月13日之间，纳入了44例患者：33例和9例复发和难治性，分别。320、480和480mg禁食组包括20、7和17名患者，分别。中位随访时间为37.1个月。总有效率为63.6%（95%CI：47.8-77.6），完全缓解（CR）。未经确认的CR，9、7和12名患者有部分反应，分别。中位反应持续时间（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)为2.9个月,分别,PFS和OS率为13.9%和56.7%，分别。不良事件发生在38例（86.4%）：23例（52.3%）中≥3级，包括1例5级事件。在接受长期治疗的患者中，KPS和生活质量（QoL）评分保持得很好。
■结果证明了替拉鲁替尼的长期临床益处，在部分患者中具有深度和持久的反应以及可接受的安全性，而KPS和QoL评分保持不变。
