Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Hematology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Cancer. 2022 Jun 1;128(11):2138-2147. doi: 10.1002/cncr.34182. Epub 2022 Mar 22.
Patients with refractory central nervous system leukemia (CNSL) have a dismal prognosis and lack effective therapy. Case reports have shown that sorafenib is effective against brain metastases, including leukemia.
To explore the efficacy of sorafenib combined with conventional therapies for refractory CNSL, a phase 2 study was conducted. The primary end point was the complete remission rate (CRR) within 8 weeks of treatment. Secondary end points included the overall response rate (ORR), event-free survival (EFS), overall survival (OS), and adverse events (AEs).
Twenty-six patients with refractory CNSL were enrolled; they included 17 with isolated CNSL, 7 with hematological relapse, and 2 with another extramedullary relapse. After 8 weeks of treatment, 21 patients achieved complete remission, 2 achieved partial remission, and 3 achieved no remission for a CRR of 80.8% (95% CI, 62.1%-91.5%) and an ORR of 88.5% (95% CI, 71.0%-96.0%). Twenty patients survived, and 6 died. The 2-year EFS and OS rates were 75.0% (95% CI, 54.5%-88.3%) and 76.9% (95% CI, 54.2%-90.4%), respectively. Six patients experienced grade 3 or 4 treatment-related AEs, including moderate chronic graft-vs-host disease (n = 3), grade 3 or 4 acute graft-vs-host disease (n = 2), and grade 3 skin rash (n = 1). No treatment-related deaths occurred during the therapy of refractory CNSL.
Sorafenib combined with conventional therapies is effective and safe for refractory CNSL.
Sorafenib combined with conventional therapies is effective and safe for refractory central nervous system leukemia.
难治性中枢神经系统白血病（CNSL）患者预后较差，缺乏有效治疗方法。病例报告显示，索拉非尼对包括白血病在内的脑转移瘤有效。
为探索索拉非尼联合常规疗法治疗难治性 CNSL 的疗效，开展了一项 2 期研究。主要终点为治疗 8 周内的完全缓解率（CRR）。次要终点包括总缓解率（ORR）、无事件生存（EFS）、总生存（OS）和不良事件（AE）。
共纳入 26 例难治性 CNSL 患者，其中孤立性 CNSL 17 例，血液学复发 7 例，另一髓外复发 2 例。治疗 8 周后，21 例患者达到完全缓解，2 例达到部分缓解，3 例未缓解，CRR 为 80.8%（95%CI，62.1%-91.5%），ORR 为 88.5%（95%CI，71.0%-96.0%）。20 例患者存活，6 例死亡。2 年 EFS 和 OS 率分别为 75.0%（95%CI，54.5%-88.3%）和 76.9%（95%CI，54.2%-90.4%）。6 例患者发生 3 或 4 级治疗相关 AE，包括中重度慢性移植物抗宿主病（n=3）、3 或 4 级急性移植物抗宿主病（n=2）和 3 级皮疹（n=1）。在难治性 CNSL 的治疗过程中，无治疗相关死亡。
索拉非尼联合常规疗法治疗难治性 CNSL 有效且安全。
索拉非尼联合常规疗法治疗难治性中枢神经系统白血病有效且安全。
