Real-world Efficacy and Safety of Flumatinib as the First-line Treatment in Patients With de novo Philadelphia-positive Acute Lymphoblastic Leukemia.

IF 2.7 4区医学 Q2 HEMATOLOGY

Clinical Lymphoma, Myeloma & Leukemia Pub Date : 2025-04-15 DOI:10.1016/j.clml.2025.04.010

Zhibo Zhang, Jia Yin, Jun Wang, Xuefeng He, Xiaohui Hu, Haiwen Huang, Limin Liu, Miao Miao, Ying Wang, Huiying Qiu, Xiaowen Tang, Depei Wu, Xiao Ma, Weiyang Li

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Abstract

Background: The real-world data of flumatinib, a China-developed second-generation tyrosine kinase inhibitors (TKI), on Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is limited. This study evaluated the efficacy and safety of flumatinib combined with chemotherapy as first-line therapy for Ph+ ALL.

Methods: This multicenter retrospective study included 65 adults with de novo Ph+ ALL treated with flumatinib (600 mg/day) plus intensive chemotherapy. Outcomes included complete remission (CR), CR with minimal residual disease negativity detected by multiparameter flow cytometry (CR _flow-), overall survival (OS), event-free survival (EFS), and adverse events (AEs). Survival and prognostic factors were analyzed using the Kaplan-Meier method.

Results: CR and CR _flow- were achieved in 96.9% (63/65) and 58.5% (38/65) of patients postinduction, respectively. At 24 months, OS and EFS were 87.4% and 62.6%, respectively. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) improved EFS (P < .0001) and tended to improve OS (P = .0503). Common hematologic AEs included neutropenia (93.8%) and thrombocytopenia (76.9%); severe nonhematologic AEs were rare. Relapses (17/63) predominantly associated with T315I (10/19) and Y253H (5/19) mutations. Age ≥ 35 years, BCR/ABL1^P210, and ABL1 Y253H mutation were significantly associated with worse OS. Meanwhile, female, ABL1 Y253H mutation, ABL1 T315I mutation, and failure with achievement of MMR after the first course of consolidation therapy were risk factors for EFS.

Conclusions: Flumatinib-based regimens demonstrated high efficacy and tolerable toxicity in Ph+ ALL, which was comparable to other second-generation TKIs. T315I and Y253H mutations were key drivers of relapse. Although allo-HSCT enhanced survival, longer follow-up period and prospective trials are warranted to validate these findings.

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氟马替尼作为新发费城阳性急性淋巴细胞白血病患者一线治疗的实际疗效和安全性

背景：氟马替尼是中国开发的第二代酪氨酸激酶抑制剂（TKI），其治疗费城染色体阳性急性淋巴细胞白血病（Ph+ ALL）的实际数据有限。本研究评价氟马替尼联合化疗作为一线治疗Ph+ ALL的疗效和安全性。方法：这项多中心回顾性研究纳入65例新发Ph+ ALL的成人患者，接受氟马替尼（600mg /天）加强化化疗。结果包括完全缓解（CR），多参数流式细胞术（CR flow-）检测到的最小残留疾病阴性的CR，总生存期（OS），无事件生存期（EFS）和不良事件（ae）。采用Kaplan-Meier法分析生存和预后因素。结果：诱导后96.9%（63/65）的患者达到CR， 58.5%（38/65）的患者达到CR流。24个月时，OS和EFS分别为87.4%和62.6%。同种异体造血干细胞移植（alloo - hsct）可改善EFS (P < 0.0001)，并有改善OS的趋势（P = 0.0503）。常见的血液学ae包括中性粒细胞减少症（93.8%）和血小板减少症（76.9%）；严重的非血液学不良反应罕见。复发（17/63）主要与T315I（10/19）和Y253H（5/19）突变相关。年龄≥35岁，BCR/ABL1P210和ABL1 Y253H突变与较差的OS显著相关。同时，女性、ABL1 Y253H突变、ABL1 T315I突变、第一疗程巩固治疗后未达到MMR是EFS的危险因素。结论：以氟马替尼为基础的方案在Ph+ ALL中表现出高疗效和可耐受的毒性，与其他第二代TKIs相当。T315I和Y253H突变是复发的关键驱动因素。尽管同种异体造血干细胞移植提高了生存率，但需要更长的随访期和前瞻性试验来验证这些发现。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Lymphoma, Myeloma & Leukemia ONCOLOGY-HEMATOLOGY

CiteScore

2.70

自引率

3.70%

发文量

1606

审稿时长

26 days

期刊介绍： Clinical Lymphoma, Myeloma & Leukemia is a peer-reviewed monthly journal that publishes original articles describing various aspects of clinical and translational research of lymphoma, myeloma and leukemia. Clinical Lymphoma, Myeloma & Leukemia is devoted to articles on detection, diagnosis, prevention, and treatment of lymphoma, myeloma, leukemia and related disorders including macroglobulinemia, amyloidosis, and plasma-cell dyscrasias. The main emphasis is on recent scientific developments in all areas related to lymphoma, myeloma and leukemia. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.