Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Guangdong Provincial Clinical Research Center for Hematologic Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
J Hematol Oncol. 2024 Oct 28;17(1):101. doi: 10.1186/s13045-024-01624-8.
Early T-cell precursor lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) is a distinct subtype of T-ALL/LBL, characterized by a poor response to initial chemotherapy, a high relapse rate, and an inferior outcome. The treatment options for ETP-ALL/LBL are currently limited, and there are no reported clinical trials available for ETP-ALL/LBL. From June 2018 to June 2022, we conducted a single-arm, single-center, phase 2 trial (NCT03553238) in newly diagnosed ETP-ALL/LBL (age 14-55). Patients (N = 54) received pediatric-inspired chemotherapy plus tucidinostat, which was orally administered once daily at a dosage of 10 mg from induction to consolidation therapy. The primary endpoint was 3 year event-free survival (EFS). Secondary endpoints were overall survival (OS), relapse-free survival (RFS), complete remission rate and adverse events. The composite complete remission (CRc, complete response [CR] plus complete response with incomplete blood count recovery [CRi]) rate and MRD negativity after induction therapy was 91% (49 of 54 patients) and 65% (35 of 54 patients), respectively. The MRD negativity after consolidation was achieved in 87% patients (47 of 54 patients). With a median follow-up of 39.3 months (IQR, 20.6 to 60.0), the 3 year EFS rate was 67.7% (95% CI 56.2-81.7), the 3 year OS rate was 71.5% (95% CI 60.2-84.9) and the 3 year RFS rate was 67.5% (95% CI 55.9-81.6). The most common grade 3-4 adverse events were neutropenia (94%), anemia (85%), thrombocytopenia (76%), and infection (53%). Tucidinostat plus pediatric regimen is an effective and well-tolerated regimen for new diagnosed ETP-ALL/LBL, with high CRc and MRD negativity rates, as well as encouraging survival outcomes.
早期 T 细胞前体细胞淋巴母细胞白血病/淋巴瘤（ETP-ALL/LBL）是 T 细胞 ALL/LBL 的一个独特亚型，其特点是对初始化疗反应不佳、复发率高、预后不良。目前 ETP-ALL/LBL 的治疗选择有限，并且没有报道针对 ETP-ALL/LBL 的临床试验。从 2018 年 6 月至 2022 年 6 月，我们在新诊断的 ETP-ALL/LBL（年龄 14-55 岁）患者中开展了一项单臂、单中心、Ⅱ期临床试验（NCT03553238）。患者（N=54）接受了儿童启发式化疗加 tucidinostat，tucidinostat 从诱导期到巩固期每日口服一次，剂量为 10mg。主要终点为 3 年无事件生存（EFS）。次要终点包括总生存（OS）、无复发生存（RFS）、完全缓解率和不良事件。诱导治疗后复合完全缓解率（CRc，完全缓解[CR]加不完全血细胞计数恢复的完全缓解[CRi]）和 MRD 阴性率分别为 91%（54 例患者中的 49 例）和 65%（54 例患者中的 35 例）。巩固后有 87%的患者达到了 MRD 阴性（54 例患者中的 47 例）。中位随访 39.3 个月（IQR，20.6-60.0），3 年 EFS 率为 67.7%（95%CI 56.2-81.7），3 年 OS 率为 71.5%（95%CI 60.2-84.9），3 年 RFS 率为 67.5%（95%CI 55.9-81.6）。最常见的 3-4 级不良事件为中性粒细胞减少（94%）、贫血（85%）、血小板减少（76%）和感染（53%）。tucidinostat 加儿童方案是新诊断的 ETP-ALL/LBL 的一种有效且耐受良好的方案，具有较高的 CRc 和 MRD 阴性率，以及令人鼓舞的生存结果。
